...1020...2829303132...405060...


BlockchainHub – Blockchain, Smart Contracts, ICOs, Tokens & Web3

Advisor: Technology

Joachim is an entrepreneur and tech enthusiast. He is obsessed with knowledge, change and innovation. Currently, he is Founder and CEO of Jolocom, a Berlin-based startup building decentralized tools that lets you generate your own digital identity to assist linkage and attribution of data. Besides that Joachim is a connector for Ouishare, curating the topic of Decentralization & Blockchain. Also he organizes GETDcent and is an active member of the Agora Collective in Berlin.

See the original post here:

BlockchainHub – Blockchain, Smart Contracts, ICOs, Tokens & Web3

Blockchain Technology and Applications | Microsoft Azure

A common blockchain pattern is IoT-enabled monitoring of an asset as it moves along a multi-party supply chain. A great example of this pattern is the refrigerated transportation of perishable goods like food or pharmaceuticals where certain compliance rules must be met throughout the duration of the transportation process. In this scenario, an initiating counterparty (such as a retailer) specifies contractual conditions, such as a required humidity and temperature range, that the custodians on the supply chain must adhere to. At any point, if the device takes a temperature or humidity measurement that is out of range, the smart contract state will be updated to indicate that it’s out of compliance, recording a transaction on the blockchain and triggering remediating events downstream.

Read more here:

Blockchain Technology and Applications | Microsoft Azure

SeaLand

Become a PRO with our online-shipping tutorials

We’re with you every step of the learning process. Get the efficient and straightforward guidance you need to perform all the function on MySeaLand. You’ll find the range of tutorials that are designed to help you master our tools and ship with us. Our tutorials include: how to register on MySeaLand, look up schedules and rates, how to create a booking, and much more.

LEARN MORE!

Original post:

SeaLand

Sealand Toilet: Parts & Accessories | eBay

eBayShop by category

Shop by category

{“modules”:[“unloadOptimization”,”bandwidthDetection”],”unloadOptimization”:{“browsers”:{“Firefox”:true,”Chrome”:true}},”bandwidthDetection”:{“url”:”https://ir.ebaystatic.com/cr/v/c1/thirtysevens.jpg”,”maxViews”:4,”imgSize”:37,”expiry”:300000,”timeout”:250}}

{“delay”:300}

The elegant 310 china toilet has everything you want a powerful, 100% bowl coverage flush, great looks and a great price. Color: White. No brokerage fees!

BREAKER,VACUUM For Traveler and Sealand Model Toilets with hand sprayers 110,111,210,211,510 ,511 ,910,911,2010,2011,3010,3011,3110,3111.

Read the original here:

Sealand Toilet: Parts & Accessories | eBay

Search for a route – sealand.com

ACMH NORTHBOUND MANZANILLO (PA) – WILLEMSTAD (CW) – ORANJESTAD (AW) – KINGSTON (JM) View Map ACMH SOUTHBOUND WILLEMSTAD (CW) – ORANJESTAD (AW) – KINGSTON (JM) – MANZANILLO (PA) View Map ACX NORTHBOUND ITAJAI (BR) – PARANAGUA (BR) – SANTOS (BR) – RIO DE JANEIRO (BR) – CARTAGENA (CO) – KINGSTON (JM) – NEW ORLEANS (US) – HOUSTON (US) – ALTAMIRA (MX) – VERACRUZ (MX) View Map ACX SOUTHBOUND NEW ORLEANS (US) – HOUSTON (US) – ALTAMIRA (MX) – VERACRUZ (MX) – KINGSTON (JM) – CARTAGENA (CO) – MANZANILLO (PA) – MANAUS (BR) – VITORIA (BR) – SANTOS (BR) – ITAJAI (BR) – PARANAGUA (BR) – SANTOS (BR) – RIO DE JANEIRO (BR) View Map CALYPSO EASTBOUND MANZANILLO (PA) – BARRANQUILLA (CO) – CARTAGENA (CO) – SANTA MARTA (CO) – POINT LISAS (TT) – GEORGETOWN (GY) – PARAMARIBO (SR) View Map CALYPSO WESTBOUND PARAMARIBO (SR) – GEORGETOWN (GY) – POINT LISAS (TT) – CARTAGENA (CO) – BARRANQUILLA (CO) – SANTA MARTA (CO) – MANZANILLO (PA) View Map CARIBBEAN WESTBOUND RIO HAINA (DO) – SAN JUAN (PR) – CAUCEDO (DO) – MANZANILLO (PA) – CARTAGENA (CO) View Map CARIBBEAN EASTBOUND MANZANILLO (PA) – CARTAGENA (CO) – CAUCEDO (DO) – RIO HAINA (DO) – SAN JUAN (PR) View Map ECUBEX NORTHBOUND GUAYAQUIL (EC) – BALBOA (PA) – MANZANILLO (PA) View Map ECUBEX SOUTHBOUND CARTAGENA (CO) – MANZANILLO (PA) – BALBOA (PA) – GUAYAQUIL (EC) View Map ECUMED NORTHBOUND BUENAVENTURA (CO) – GUAYAQUIL (EC) – BALBOA (PA) – MANZANILLO (PA) View Map ECUMED SOUTHBOUND NEWARK (US) – MANZANILLO (PA) – BUENAVENTURA (CO) – GUAYAQUIL (EC) – BALBOA (PA) – MANZANILLO (PA) View Map GUANTA EASTBOUND KINGSTON (JM) – MANZANILLO (PA) – GUANTA (VE) View Map GUANTA WESTBOUND GUANTA (VE) – KINGSTON (JM) – MANZANILLO (PA) View Map GULFEX NORTHBOUND RIO GRANDE (BR) – NAVEGANTES (BR) – SANTOS (BR) – RIO DE JANEIRO (BR) – CARTAGENA (CO) – VERACRUZ (MX) – ALTAMIRA (MX) – HOUSTON (US) – NEW ORLEANS (US) View Map GULFEX SOUTHBOUND VERACRUZ (MX) – ALTAMIRA (MX) – HOUSTON (US) – NEW ORLEANS (US) – CARTAGENA (CO) – SUAPE (BR) – SANTOS (BR) – RIO GRANDE (BR) – NAVEGANTES (BR) – RIO DE JANEIRO (BR) View Map JAMAICA-HAITI NORTHBOUND MANZANILLO (PA) – KINGSTON (JM) – PORT-AU-PRINCE (HT) View Map JAMAICA-HAITI SOUTHBOUND KINGSTON (JM) – PORT-AU-PRINCE (HT) – MANZANILLO (PA) View Map MARACAIBO EASTBOUND MANZANILLO (PA) – KINGSTON (JM) – GUARANAO (VE) – MARACAIBO (VE) View Map MARACAIBO WESTBOUND GUARANAO (VE) – MARACAIBO (VE) – MANZANILLO (PA) – KINGSTON (JM) View Map NAE NORTHBOUND CARTAGENA (CO) – TURBO (CO) – MANZANILLO (PA) – PUERTO MOIN (CR) – PHILADELPHIA (US) – NEW YORK (US) – SAVANNAH (US) – PORT EVERGLADES (US) View Map NAE SOUTHBOUND PHILADELPHIA (US) – NEW YORK (US) – SAVANNAH (US) – PORT EVERGLADES (US) – CARTAGENA (CO) – TURBO (CO) – MANZANILLO (PA) – PUERTO MOIN (CR) View Map OCEANIA NORTHBOUND MANZANILLO (PA) – CRISTOBAL (PA) – CARTAGENA (CO) – PHILADELPHIA (US) – CHARLESTON (US) View Map OCEANIA SOUTHBOUND PHILADELPHIA (US) – CHARLESTON (US) – CARTAGENA (CO) – BALBOA (PA) View Map SLING 2 NORTHBOUND BUENOS AIRES (AR) – MONTEVIDEO (UY) – RIO GRANDE (BR) – NAVEGANTES (BR) View Map SLING 2 SOUTHBOUND NAVEGANTES (BR) – BUENOS AIRES (AR) – MONTEVIDEO (UY) – RIO GRANDE (BR) View Map SAE NORTHBOUND MANZANILLO (PA) – PUERTO CORTES (HN) – SANTO TOMAS (GT) – PORT EVERGLADES (US) – WILMINGTON (US) – NORFOLK (US) – PHILADELPHIA (US) – SAVANNAH (US) View Map SAE SOUTHBOUND NORFOLK (US) – PHILADELPHIA (US) – WILMINGTON (US) – SAVANNAH (US) – PORT EVERGLADES (US) – SANTO TOMAS (GT) – PUERTO CORTES (HN) – MANZANILLO (PA) View Map VENEZUELA EASTBOUND (LAG) MANZANILLO (PA) – LA GUAIRA (VE) – CARTAGENA (CO) – CRISTOBAL (PA) – TURBO (CO) View Map VENEZUELA WESTBOUND (LAG) CARTAGENA (CO) – CRISTOBAL (PA) – TURBO (CO) – MANZANILLO (PA) – LA GUAIRA (VE) View Map VENEZUELA EASTBOUND (PBL) MANZANILLO (PA) – CARTAGENA (CO) – PUERTO CABELLO (VE) View Map VENEZUELA WESTBOUND (PBL) PUERTO CABELLO (VE) – MANZANILLO (PA) – CARTAGENA (CO) View Map

Original post:

Search for a route – sealand.com

Sealand | Hetalia Archives | FANDOM powered by Wikia

‘Sealand (, Shrando) is a character in the popular manga and anime series, Hetalia: Axis Powers. In 2008, Himaruya gave human names to some of the characters and he received the name P’eter Kirkland(, Pt Kkurando).

He has blond hair, blue eyes, and thick eyebrows much likeEngland’s. He wears a white sailor shirt with a blue collar, a blue neck tie, a matching hat, and blue capri pants, as well as white knee-high socks and black Mary Jane shoes.

Originally, Sealand’s eyebrows were drawn somewhat thinner, while his sailor necktie lacked its “tails”, and he wore shorts instead of capris. His eyes were also originally colored green, giving him a further resemblance to a younger England.

In the gameNoto-sama 6, his hair is colored a dark sandy blond, while his eyes are sea green.

Due to the fact that he isn’t considered an actual nation, none of the others take him very seriously. However, Sealand believes that someday he will become a huge empire that even his brother will bow down to.

Like his fort, he is actually made of steel and can fire a “Rocket Punch” that he believes is super powerful (though in actuality he can only do so when dressed up in a kids’ mecha costume). He also tends to end his sentences with “desu yo”, which is meant to give him a very enthusiastic flare.

Sealand declared himself an independent country when England didn’t want it back after the end of the war. The two always bicker because Sealand, who wants to be recognized as a nation, often sneaks into conferences the other countries attend (such as the G8, when Sealand pretended to be Canada). Despite calling his brother “Jerk England” and promising that the older nation will bow to him someday, Sealand relies on England.

Sealand first met him when Iceland was attempting to auction himself off on Ebay, but Iceland didn’t understand what he meant when he wanted to become his friend due to their similarities, (as well as Sealand wanting to be referred to as “senpai” by Iceland.)

The two are good friends, in part due to their similarities of being small nations that don’t get the respect that they want (though Latvia is an actual recognized nation in comparison to Sealand being a micronation). However, while Latvia attempts to act as a big brother to Sealand, his own insecurities get in the way, most notably his fear of Russia.

After being auctioned off online, Sealand became his property and adoptive child (as Sweden was the only one that bid). The two appear to have a close relationship, though Sweden came up with the strange idea of a “Dambolis” in an attempt to make the TV-obsessed Sealand pay attention to him more.

Sealand attempts to make friends with TRNC and points out that they are both micronations, but TRNC blows him off and points out that while he is recognized by Turkey, Sealand is recognized by no one. Sealand begins to cry, and he later attacks TRNC in a fit of rage. After Sealand becomes friends with Wy and Seborga, TRNC is seen watching them from a distance.

Sealand has tried to make friends with the Australian micronation of Wy, based on percieved similarities. Wy quickly pointed out that unlike Sealand, she is recognized, as Wy’s declaration of independence was accepted by the mayor of the surrounding township in 2004.

Sealand first appears in Episode 21, which adapts It’s Sealand-kun! (reprinted as Recommend! Sealand! in Hetalia:Axis Powers volume 1). He attempts to attend a world meeting with the other nations, though his presence winds up going ignored. Sealand managed to get Japan to notice and nod his head toward him (Japan

Sealand’s appearance in Episode 21

then turned around and continued walking in the direction he was heading), but it was seen that Japan looked rather uncomfortable and England stared at Japan with a harsh look. Sealand manages to get Lithuania to notice him, and is given advice on how to become an actual nation.

In the anime, his eyebrows are drawn thinner and earlier character design is used, with the exception of his eyes being colored blue as in his later design.

While the exact origin of his human name is unknown, ‘P’eter means “rock” and could possibly be a reference to the fact that the actual Sealand is simply a “rock” itself, or more accurately, a small concrete military fort. Another common assumption is that his name is referencing Peter Pan, due to his inability to grow up, and he shares his surname with his older brother, England.

Marukaite Chikyuu (Sealand)

SEALAND RELEVANT

Read more:

Sealand | Hetalia Archives | FANDOM powered by Wikia

Sealand | West Marine

{{if false }} {{if recVal[‘Product.outletNewUntilFlag’] && recVal[‘Product.outletNewUntilFlag’][0] == ‘New Arrivals’ }} New Arrival {{else recVal[‘Product.specialBuyFlag’] && recVal[‘Product.specialBuyFlag’][0] == ‘Yes’ }} Special Buy {{else recVal[‘Product.exclusiveFlag’] && recVal[‘Product.exclusiveFlag’][0] == ‘true’ }} Exclusive {{/if}} {{else false }} {{if recVal[‘Product.newItemFlag’] && recVal[‘Product.newItemFlag’][0] == ‘New’ }} New {{else recVal[‘Product.wmClearanceFlag’] && recVal[‘Product.wmClearanceFlag’][0] == ‘Clearance’ }} Clearance {{else recVal[‘Product.exclusiveFlag’] && recVal[‘Product.exclusiveFlag’][0] == ‘true’ }} Exclusive {{/if}} {{else false }} {{if recVal[‘Product.saleFlagOverlay’] && recVal[‘Product.saleFlagOverlay’][0] == ‘Yes’ }} Sale {{else recVal[‘Product.rebateAvailableFlag’] && recVal[‘Product.rebateAvailableFlag’][0] == ‘true’ }} Rebate {{else recVal[‘Product.wmClearanceFlag’] && recVal[‘Product.wmClearanceFlag’][0] == ‘Clearance’ }} Clearance {{else recVal[‘Product.specialBuyFlag’] && recVal[‘Product.specialBuyFlag’][0] == ‘Yes’ }} Special Buy {{else recVal[‘Product.exclusiveFlag’] && recVal[‘Product.exclusiveFlag’][0] == ‘true’ }} Exclusive {{/if}} {{else}} {{if recVal[‘Product.saleFlagOverlay’] && recVal[‘Product.saleFlagOverlay’][0] == ‘Yes’ }} Sale {{else recVal[‘Product.newItemFlag’] && recVal[‘Product.newItemFlag’][0] == ‘New’ }} New {{else recVal[‘Product.rebateAvailableFlag’] && recVal[‘Product.rebateAvailableFlag’][0] == ‘true’ }} Rebate {{else recVal[‘Product.wmClearanceFlag’] && recVal[‘Product.wmClearanceFlag’][0] == ‘Clearance’ }} Clearance {{else recVal[‘Product.specialBuyFlag’] && recVal[‘Product.specialBuyFlag’][0] == ‘Yes’ }} Special Buy {{else recVal[‘Product.exclusiveFlag’] && recVal[‘Product.exclusiveFlag’][0] == ‘true’ }} Exclusive {{/if}} {{/if}}

Read the original:

Sealand | West Marine

Sealand Marine Toilet Parts | West Marine

{{if false }} {{if recVal[‘Product.outletNewUntilFlag’] && recVal[‘Product.outletNewUntilFlag’][0] == ‘New Arrivals’ }} New Arrival {{else recVal[‘Product.specialBuyFlag’] && recVal[‘Product.specialBuyFlag’][0] == ‘Yes’ }} Special Buy {{else recVal[‘Product.exclusiveFlag’] && recVal[‘Product.exclusiveFlag’][0] == ‘true’ }} Exclusive {{/if}} {{else false }} {{if recVal[‘Product.newItemFlag’] && recVal[‘Product.newItemFlag’][0] == ‘New’ }} New {{else recVal[‘Product.wmClearanceFlag’] && recVal[‘Product.wmClearanceFlag’][0] == ‘Clearance’ }} Clearance {{else recVal[‘Product.exclusiveFlag’] && recVal[‘Product.exclusiveFlag’][0] == ‘true’ }} Exclusive {{/if}} {{else false }} {{if recVal[‘Product.saleFlagOverlay’] && recVal[‘Product.saleFlagOverlay’][0] == ‘Yes’ }} Sale {{else recVal[‘Product.rebateAvailableFlag’] && recVal[‘Product.rebateAvailableFlag’][0] == ‘true’ }} Rebate {{else recVal[‘Product.wmClearanceFlag’] && recVal[‘Product.wmClearanceFlag’][0] == ‘Clearance’ }} Clearance {{else recVal[‘Product.specialBuyFlag’] && recVal[‘Product.specialBuyFlag’][0] == ‘Yes’ }} Special Buy {{else recVal[‘Product.exclusiveFlag’] && recVal[‘Product.exclusiveFlag’][0] == ‘true’ }} Exclusive {{/if}} {{else}} {{if recVal[‘Product.saleFlagOverlay’] && recVal[‘Product.saleFlagOverlay’][0] == ‘Yes’ }} Sale {{else recVal[‘Product.newItemFlag’] && recVal[‘Product.newItemFlag’][0] == ‘New’ }} New {{else recVal[‘Product.rebateAvailableFlag’] && recVal[‘Product.rebateAvailableFlag’][0] == ‘true’ }} Rebate {{else recVal[‘Product.wmClearanceFlag’] && recVal[‘Product.wmClearanceFlag’][0] == ‘Clearance’ }} Clearance {{else recVal[‘Product.specialBuyFlag’] && recVal[‘Product.specialBuyFlag’][0] == ‘Yes’ }} Special Buy {{else recVal[‘Product.exclusiveFlag’] && recVal[‘Product.exclusiveFlag’][0] == ‘true’ }} Exclusive {{/if}} {{/if}}

Visit link:

Sealand Marine Toilet Parts | West Marine

Sealand Vacuflush: Boat Parts | eBay

eBayShop by category

Shop by category

{“modules”:[“unloadOptimization”,”bandwidthDetection”],”unloadOptimization”:{“browsers”:{“Firefox”:true,”Chrome”:true}},”bandwidthDetection”:{“url”:”https://ir.ebaystatic.com/cr/v/c1/thirtysevens.jpg”,”maxViews”:4,”imgSize”:37,”expiry”:300000,”timeout”:250}}

{“delay”:300}

Was installed in a cramped space onboard so was seldom used.

$500.00

Buy It Now

or Best Offer

Free Shipping

The clean, odor-free performance of VacuFlush 5000 series toilets is the result of freshwater flushing, instantaneous evacuation of bowl contents, and thorough rinsing action. For VacuFlush systems (c…

Read the original post:

Sealand Vacuflush: Boat Parts | eBay

Sea-Steading: A Life of Hope and Freedom on the Last …

‘).appendTo(flyout.elem());var panelGroup=flyout.getName()+’SubCats’;var hideTimeout=null;var sloppyTrigger=createSloppyTrigger($parent);var showParent=function(){if(hideTimeout){clearTimeout(hideTimeout);hideTimeout=null;} if(visible){return;} var height=$(‘#nav-flyout-shopAll’).height(); $parent.css({‘height’: height});$parent.animate({width:’show’},{duration:200,complete:function(){$parent.css({overflow:’visible’});}});visible=true;};var hideParentNow=function(){$parent.stop().css({overflow:’hidden’,display:’none’,width:’auto’,height:’auto’});panels.hideAll({group:panelGroup});visible=false;if(hideTimeout){clearTimeout(hideTimeout);hideTimeout=null;}};var hideParent=function(){if(!visible){return;} if(hideTimeout){clearTimeout(hideTimeout);hideTimeout=null;} hideTimeout=setTimeout(hideParentNow,10);};flyout.onHide(function(){sloppyTrigger.disable();hideParentNow();this.elem().hide();});var addPanel=function($link,panelKey){var panel=dataPanel({className:’nav-subcat’,dataKey:panelKey,groups:[panelGroup],spinner:false,visible:false});if(!flyoutDebug){var mouseout=mouseOutUtility();mouseout.add(flyout.elem());mouseout.action(function(){panel.hide();});mouseout.enable();} var a11y=a11yHandler({link:$link,onEscape:function(){panel.hide();$link.focus();}});var logPanelInteraction=function(promoID,wlTriggers){var logNow=$F.once().on(function(){var panelEvent=$.extend({},event,{id:promoID});if(config.browsePromos&&!!config.browsePromos[promoID]){panelEvent.bp=1;} logEvent(panelEvent);phoneHome.trigger(wlTriggers);});if(panel.isVisible()&&panel.hasInteracted()){logNow();}else{panel.onInteract(logNow);}};panel.onData(function(data){renderPromo(data.promoID,panel.elem());logPanelInteraction(data.promoID,data.wlTriggers);});panel.onShow(function(){var columnCount=$(‘.nav-column’,panel.elem()).length;panel.elem().addClass(‘nav-colcount-‘+columnCount);showParent();var $subCatLinks=$(‘.nav-subcat-links > a’,panel.elem());var length=$subCatLinks.length;if(length>0){var firstElementLeftPos=$subCatLinks.eq(0).offset().left;for(var i=1;i’+ catTitle+”);panel.elem().prepend($subPanelTitle);}} $link.addClass(‘nav-active’);});panel.onHide(function(){$link.removeClass(‘nav-active’);hideParent();a11y.disable();sloppyTrigger.disable();});panel.onShow(function(){a11y.elems($(‘a, area’,panel.elem()));});sloppyTrigger.register($link,panel);if(flyoutDebug){$link.click(function(){if(panel.isVisible()){panel.hide();}else{panel.show();}});} var panelKeyHandler=onKey($link,function(){if(this.isEnter()||this.isSpace()){panel.show();}},’keydown’,false);$link.focus(function(){panelKeyHandler.bind();}).blur(function(){panelKeyHandler.unbind();});panel.elem().appendTo($parent);};var hideParentAndResetTrigger=function(){hideParent();sloppyTrigger.disable();};for(var i=0;i

Enter your mobile number or email address below and we’ll send you a link to download the free Kindle App. Then you can start reading Kindle books on your smartphone, tablet, or computer – no Kindle device required.

$20.85 +Free Shipping

Sold by: Wordery Specialist

$16.87 +$3.99shipping

Sold by: awesomebooksusa

$22.88 +Free Shipping

Sold by: Bahamut Media

Flip to back Flip to front

See original here:

Sea-Steading: A Life of Hope and Freedom on the Last …

Ocean colonization – Wikipedia

Ocean colonization or ocean colonisation is the theory and practice of permanent human settlement of oceans. Such settlements may be seasteads floating on the surface of the water, or exist as underwater habitats secured to the ocean floor, or in an intermediate position.

One primary purpose of ocean colonization is the expansion of livable area. Other possible benefits include expanded access to undersea resources, novel forms of governance (for instance micronations), and new recreational activities.

Lessons learned from ocean colonization may prove applicable to space colonization. The ocean may prove simpler to colonize than space and thus occur first, providing a proving ground for the latter. In particular, the issue of sovereignty may bear many similarities between ocean and space colonization; adjustments to social life under harsher circumstances would apply similarly to the ocean and to space; and many technologies may have uses in both environments.

[1][2]

Read the rest here:

Ocean colonization – Wikipedia

Stem-cell therapy – Wikipedia

This article is about the medical therapy. For the cell type, see Stem cell.

Stem-cell therapy is the use of stem cells to treat or prevent a disease or condition.[1]

Bone marrow transplant is the most widely used stem-cell therapy, but some therapies derived from umbilical cord blood are also in use. Research is underway to develop various sources for stem cells, as well as to apply stem-cell treatments for neurodegenerative diseases and conditions such as diabetes and heart disease, among others.

Stem-cell therapy has become controversial following developments such as the ability of scientists to isolate and culture embryonic stem cells, to create stem cells using somatic cell nuclear transfer and their use of techniques to create induced pluripotent stem cells. This controversy is often related to abortion politics and to human cloning. Additionally, efforts to market treatments based on transplant of stored umbilical cord blood have been controversial.

For over 30 years, bone marrow has been used to treat people with cancer with conditions such as leukaemia and lymphoma; this is the only form of stem-cell therapy that is widely practiced.[2][3][4] During chemotherapy, most growing cells are killed by the cytotoxic agents. These agents, however, cannot discriminate between the leukaemia or neoplastic cells, and the hematopoietic stem cells within the bone marrow. It is this side effect of conventional chemotherapy strategies that the stem-cell transplant attempts to reverse; a donor’s healthy bone marrow reintroduces functional stem cells to replace the cells lost in the host’s body during treatment. The transplanted cells also generate an immune response that helps to kill off the cancer cells; this process can go too far, however, leading to graft vs host disease, the most serious side effect of this treatment.[5]

Another stem-cell therapy called Prochymal, was conditionally approved in Canada in 2012 for the management of acute graft-vs-host disease in children who are unresponsive to steroids.[6] It is an allogenic stem therapy based on mesenchymal stem cells (MSCs) derived from the bone marrow of adult donors. MSCs are purified from the marrow, cultured and packaged, with up to 10,000 doses derived from a single donor. The doses are stored frozen until needed.[7]

The FDA has approved five hematopoietic stem-cell products derived from umbilical cord blood, for the treatment of blood and immunological diseases.[8]

In 2014, the European Medicines Agency recommended approval of limbal stem cells for people with severe limbal stem cell deficiency due to burns in the eye.[9]

Stem cells are being studied for a number of reasons. The molecules and exosomes released from stem cells are also being studied in an effort to make medications.[10] The paracrine soluble factors produced by stem cells, known as the stem cell secretome, has been found to be the predominant mechanism by which stem cell-based therapies mediate their effects in degenerative, auto-immune and inflammatory diseases.[11]

Research has been conducted on the effects of stem cells on animal models of brain degeneration, such as in Parkinson’s, Amyotrophic lateral sclerosis, and Alzheimer’s disease.[12][13][14] There have been preliminary studies related to multiple sclerosis.[15][16]

Healthy adult brains contain neural stem cells which divide to maintain general stem-cell numbers, or become progenitor cells. In healthy adult laboratory animals, progenitor cells migrate within the brain and function primarily to maintain neuron populations for olfaction (the sense of smell). Pharmacological activation of endogenous neural stem cells has been reported to induce neuroprotection and behavioral recovery in adult rat models of neurological disorder.[17][18][19]

Stroke and traumatic brain injury lead to cell death, characterized by a loss of neurons and oligodendrocytes within the brain. Clinical and animal studies have been conducted into the use of stem cells in cases of spinal cord injury.[20][21][22]

Stem cells are studied in people with severe heart disease.[23] The work by Bodo-Eckehard Strauer[24] was discredited by identifying hundreds of factual contradictions.[25] Among several clinical trials reporting that adult stem cell therapy is safe and effective, actual evidence of benefit has been reported from only a few studies.[26] Some preliminary clinical trials achieved only modest improvements in heart function following use of bone marrow stem cell therapy.[27][28]

Stem-cell therapy for treatment of myocardial infarction usually makes use of autologous bone marrow stem cells, but other types of adult stem cells may be used, such as adipose-derived stem cells.[29]

Possible mechanisms of recovery include:[12]

In 2013, studies of autologous bone marrow stem cells on ventricular function were found to contain “hundreds” of discrepancies.[30] Critics report that of 48 reports there seemed to be just five underlying trials, and that in many cases whether they were randomized or merely observational accepter-versus-rejecter, was contradictory between reports of the same trial. One pair of reports of identical baseline characteristics and final results, was presented in two publications as, respectively, a 578 patient randomized trial and as a 391 subject observational study. Other reports required (impossible) negative standard deviations in subsets of people, or contained fractional subjects, negative NYHA classes. Overall there were many more people published as having receiving stem cells in trials, than the number of stem cells processed in the hospital’s laboratory during that time. A university investigation, closed in 2012 without reporting, was reopened in July 2013.[31]

In 2014, a meta-analysis on stem cell therapy using bone marrow stem cells for heart disease revealed discrepancies in published clinical trial reports, whereby studies with a higher number of discrepancies showed an increase in effect sizes.[32] Another meta-analysis based on the intra-subject data of 12 randomised trials was unable to find any significant benefits of stem cell therapy on primary endpoints, such as major adverse events or increase in heart function measures, concluding there was no benefit.[33]

The TIME trial, which used a randomised, double blind, placebo-controlled trial design, concluded that “bone marrow mononuclear cells administration did not improve recovery of LV function over 2 years” in people who had a myocardial infarction.[34] Accordingly, the BOOST-2 trial conducted in 10 medical centres in Germany and Norway reported that the trial result “does not support the use of nucleated BMCs in patients with STEMI and moderately reduced LVEF”.[35] Furthermore, the trial also did not meet any other secondary MRI endpoints,[36] leading to a conclusion that intracoronary bone marrow stem cell therapy does not offer a functional or clinical benefit.[37]

The specificity of the human immune-cell repertoire is what allows the human body to defend itself from rapidly adapting antigens. However, the immune system is vulnerable to degradation upon the pathogenesis of disease, and because of the critical role that it plays in overall defense, its degradation is often fatal to the organism as a whole. Diseases of hematopoietic cells are diagnosed and classified via a subspecialty of pathology known as hematopathology. The specificity of the immune cells is what allows recognition of foreign antigens, causing further challenges in the treatment of immune disease. Identical matches between donor and recipient must be made for successful transplantation treatments, but matches are uncommon, even between first-degree relatives. Research using both hematopoietic adult stem cells and embryonic stem cells has provided insight into the possible mechanisms and methods of treatment for many of these ailments.[citation needed]

Fully mature human red blood cells may be generated ex vivo by hematopoietic stem cells (HSCs), which are precursors of red blood cells. In this process, HSCs are grown together with stromal cells, creating an environment that mimics the conditions of bone marrow, the natural site of red-blood-cell growth. Erythropoietin, a growth factor, is added, coaxing the stem cells to complete terminal differentiation into red blood cells.[38] Further research into this technique should have potential benefits to gene therapy, blood transfusion, and topical medicine.

In 2004, scientists at King’s College London discovered a way to cultivate a complete tooth in mice[39] and were able to grow bioengineered teeth stand-alone in the laboratory. Researchers are confident that the tooth regeneration technology can be used to grow live teeth in people.

In theory, stem cells taken from the patient could be coaxed in the lab turning into a tooth bud which, when implanted in the gums, will give rise to a new tooth, and would be expected to be grown in a time over three weeks.[40] It will fuse with the jawbone and release chemicals that encourage nerves and blood vessels to connect with it. The process is similar to what happens when humans grow their original adult teeth. Many challenges remain, however, before stem cells could be a choice for the replacement of missing teeth in the future.[41][42]

Heller has reported success in re-growing cochlea hair cells with the use of embryonic stem cells.[43]

Since 2003, researchers have successfully transplanted corneal stem cells into damaged eyes to restore vision. “Sheets of retinal cells used by the team are harvested from aborted fetuses, which some people find objectionable.” When these sheets are transplanted over the damaged cornea, the stem cells stimulate renewed repair, eventually restore vision.[44] The latest such development was in June 2005, when researchers at the Queen Victoria Hospital of Sussex, England were able to restore the sight of forty people using the same technique. The group, led by Sheraz Daya, was able to successfully use adult stem cells obtained from the patient, a relative, or even a cadaver. Further rounds of trials are ongoing.[45]

People with diabetes lose the function of insulin-producing beta cells within the pancreas.[46] In recent experiments, scientists have been able to coax embryonic stem cell to turn into beta cells in the lab. In theory if the beta cell is transplanted successfully, they will be able to replace malfunctioning ones in a diabetic patient.[47]

Clinical case reports in the treatment orthopaedic conditions have been reported. To date, the focus in the literature for musculoskeletal care appears to be on mesenchymal stem cells. Centeno et al. have published MRI evidence of increased cartilage and meniscus volume in individual human subjects.[48][unreliable medical source?][49] The results of trials that include a large number of subjects, are yet to be published. However, a published safety study conducted in a group of 227 subjects over a 3-4-year period shows adequate safety and minimal complications associated with mesenchymal cell transplantation.[50]

Wakitani has also published a small case series of nine defects in five knees involving surgical transplantation of mesenchymal stem cells with coverage of the treated chondral defects.[51]

Stem cells can also be used to stimulate the growth of human tissues. In an adult, wounded tissue is most often replaced by scar tissue, which is characterized in the skin by disorganized collagen structure, loss of hair follicles and irregular vascular structure. In the case of wounded fetal tissue, however, wounded tissue is replaced with normal tissue through the activity of stem cells.[52] A possible method for tissue regeneration in adults is to place adult stem cell “seeds” inside a tissue bed “soil” in a wound bed and allow the stem cells to stimulate differentiation in the tissue bed cells. This method elicits a regenerative response more similar to fetal wound-healing than adult scar tissue formation.[52] Researchers are still investigating different aspects of the “soil” tissue that are conducive to regeneration.[52]

Culture of human embryonic stem cells in mitotically inactivated porcine ovarian fibroblasts (POF) causes differentiation into germ cells (precursor cells of oocytes and spermatozoa), as evidenced by gene expression analysis.[53]

Human embryonic stem cells have been stimulated to form Spermatozoon-like cells, yet still slightly damaged or malformed.[54] It could potentially treat azoospermia.

In 2012, oogonial stem cells were isolated from adult mouse and human ovaries and demonstrated to be capable of forming mature oocytes.[55] These cells have the potential to treat infertility.

Destruction of the immune system by the HIV is driven by the loss of CD4+ T cells in the peripheral blood and lymphoid tissues. Viral entry into CD4+ cells is mediated by the interaction with a cellular chemokine receptor, the most common of which are CCR5 and CXCR4. Because subsequent viral replication requires cellular gene expression processes, activated CD4+ cells are the primary targets of productive HIV infection.[56] Recently scientists have been investigating an alternative approach to treating HIV-1/AIDS, based on the creation of a disease-resistant immune system through transplantation of autologous, gene-modified (HIV-1-resistant) hematopoietic stem and progenitor cells (GM-HSPC).[57]

Stem cells are thought to mediate repair via five primary mechanisms: 1) providing an anti-inflammatory effect, 2) homing to damaged tissues and recruiting other cells, such as endothelial progenitor cells, that are necessary for tissue growth, 3) supporting tissue remodeling over scar formation, 4) inhibiting apoptosis, and 5) differentiating into bone, cartilage, tendon, and ligament tissue.[58][59]

To further enrich blood supply to the damaged areas, and consequently promote tissue regeneration, platelet-rich plasma could be used in conjunction with stem cell transplantation.[60][61] The efficacy of some stem cell populations may also be affected by the method of delivery; for instance, to regenerate bone, stem cells are often introduced in a scaffold where they produce the minerals necessary for generation of functional bone.[60][61][62][63]

Stem cells have also been shown to have a low immunogenicity due to the relatively low number of MHC molecules found on their surface. In addition, they have been found to secrete chemokines that alter the immune response and promote tolerance of the new tissue. This allows for allogeneic treatments to be performed without a high rejection risk.[64]

The ability to grow up functional adult tissues indefinitely in culture through Directed differentiation creates new opportunities for drug research. Researchers are able to grow up differentiated cell lines and then test new drugs on each cell type to examine possible interactions in vitro before performing in vivo studies. This is critical in the development of drugs for use in veterinary research because of the possibilities of species specific interactions. The hope is that having these cell lines available for research use will reduce the need for research animals used because effects on human tissue in vitro will provide insight not normally known before the animal testing phase.[65]

Stem cells are being explored for use in conservation efforts. Spermatogonial stem cells have been harvested from a rat and placed into a mouse host and fully mature sperm were produced with the ability to produce viable offspring. Currently research is underway to find suitable hosts for the introduction of donor spermatogonial stem cells. If this becomes a viable option for conservationists, sperm can be produced from high genetic quality individuals who die before reaching sexual maturity, preserving a line that would otherwise be lost.[66]

Most stem cells intended for regenerative therapy are generally isolated either from the patient’s bone marrow or from adipose tissue.[61][63] Mesenchymal stem cells can differentiate into the cells that make up bone, cartilage, tendons, and ligaments, as well as muscle, neural and other progenitor tissues, they have been the main type of stem cells studied in the treatment of diseases affecting these tissues.[67][68] The number of stem cells transplanted into damaged tissue may alter efficacy of treatment. Accordingly, stem cells derived from bone marrow aspirates, for instance, are cultured in specialized laboratories for expansion to millions of cells.[61][63] Although adipose-derived tissue also requires processing prior to use, the culturing methodology for adipose-derived stem cells is not as extensive as that for bone marrow-derived cells.[69][70] While it is thought that bone-marrow derived stem cells are preferred for bone, cartilage, ligament, and tendon repair, others believe that the less challenging collection techniques and the multi-cellular microenvironment already present in adipose-derived stem cell fractions make the latter the preferred source for autologous transplantation.[60]

New sources of mesenchymal stem cells are being researched, including stem cells present in the skin and dermis which are of interest because of the ease at which they can be harvested with minimal risk to the animal.[71] Hematopoetic stem cells have also been discovered to be travelling in the blood stream and possess equal differentiating ability as other mesenchymal stem cells, again with a very non-invasive harvesting technique.[72]

There is widespread controversy over the use of human embryonic stem cells. This controversy primarily targets the techniques used to derive new embryonic stem cell lines, which often requires the destruction of the blastocyst. Opposition to the use of human embryonic stem cells in research is often based on philosophical, moral, or religious objections.[73] There is other stem cell research that does not involve the destruction of a human embryo, and such research involves adult stem cells, amniotic stem cells, and induced pluripotent stem cells.

On 23 January 2009, the US Food and Drug Administration gave clearance to Geron Corporation for the initiation of the first clinical trial of an embryonic stem-cell-based therapy on humans. The trial aimed evaluate the drug GRNOPC1, embryonic stem cell-derived oligodendrocyte progenitor cells, on people with acute spinal cord injury. The trial was discontinued in November 2011 so that the company could focus on therapies in the “current environment of capital scarcity and uncertain economic conditions”.[74] In 2013 biotechnology and regenerative medicine company BioTime (AMEX:BTX) acquired Geron’s stem cell assets in a stock transaction, with the aim of restarting the clinical trial.[75]

Scientists have reported that MSCs when transfused immediately within few hours post thawing may show reduced function or show decreased efficacy in treating diseases as compared to those MSCs which are in log phase of cell growth(fresh), so cryopreserved MSCs should be brought back into log phase of cell growth in invitro culture before these are administered for clinical trials or experimental therapies, re-culturing of MSCs will help in recovering from the shock the cells get during freezing and thawing. Various clinical trials on MSCs have failed which used cryopreserved product immediately post thaw as compared to those clinical trials which used fresh MSCs.[76]

Research has been conducted on horses, dogs, and cats can benefit the development of stem cell treatments in veterinary medicine and can target a wide range of injuries and diseases such as myocardial infarction, stroke, tendon and ligament damage, osteoarthritis, osteochondrosis and muscular dystrophy both in large animals, as well as humans.[77][78][79][80] While investigation of cell-based therapeutics generally reflects human medical needs, the high degree of frequency and severity of certain injuries in racehorses has put veterinary medicine at the forefront of this novel regenerative approach.[81] Companion animals can serve as clinically relevant models that closely mimic human disease.[82][83]

Veterinary applications of stem cell therapy as a means of tissue regeneration have been largely shaped by research that began with the use of adult-derived mesenchymal stem cells to treat animals with injuries or defects affecting bone, cartilage, ligaments and/or tendons.[84][67][85] There are two main categories of stem cells used for treatments: allogeneic stem cells derived from a genetically different donor within the same species[63][86] and autologous mesenchymal stem cells, derived from the patient prior to use in various treatments.[60] A third category, xenogenic stem cells, or stem cells derived from different species, are used primarily for research purposes, especially for human treatments.[65]

Bone has a unique and well documented natural healing process that normally is sufficient to repair fractures and other common injuries. Misaligned breaks due to severe trauma, as well as treatments like tumor resections of bone cancer, are prone to improper healing if left to the natural process alone. Scaffolds composed of natural and artificial components are seeded with mesenchymal stem cells and placed in the defect. Within four weeks of placing the scaffold, newly formed bone begins to integrate with the old bone and within 32 weeks, full union is achieved.[87] Further studies are necessary to fully characterize the use of cell-based therapeutics for treatment of bone fractures.

Stem cells have been used to treat degenerative bone diseases. The normally recommended treatment for dogs that have LeggCalvePerthes disease is to remove the head of the femur after the degeneration has progressed. Recently, mesenchymal stem cells have been injected directly in to the head of the femur, with success not only in bone regeneration, but also in pain reduction.[87]

Because of the general positive healing capabilities of stem cells, they have gained interest for the treatment of cutaneous wounds. This is important interest for those with reduced healing capabilities, like diabetics and those undergoing chemotherapy. In one trial, stem cells were isolated from the Wharton’s jelly of the umbilical cord. These cells were injected directly into the wounds. Within a week, full re-epithelialization of the wounds had occurred, compared to minor re-epithelialization in the control wounds. This showed the capabilities of mesenchymal stem cells in the repair of epidermal tissues.[88]

Soft-palate defects in horses are caused by a failure of the embryo to fully close at the midline during embryogenesis. These are often not found until after they have become worse because of the difficulty in visualizing the entire soft palate. This lack of visualization is thought to also contribute to the low success rate in surgical intervention to repair the defect. As a result, the horse often has to be euthanized. Recently, the use of mesenchymal stem cells has been added to the conventional treatments. After the surgeon has sutured the palate closed, autologous mesenchymal cells are injected into the soft palate. The stem cells were found to be integrated into the healing tissue especially along the border with the old tissue. There was also a large reduction in the number of inflammatory cells present, which is thought to aid in the healing process.[89]

Autologous stem cell-based treatments for ligament injury, tendon injury, osteoarthritis, osteochondrosis, and sub-chondral bone cysts have been commercially available to practicing veterinarians to treat horses since 2003 in the United States and since 2006 in the United Kingdom. Autologous stem cell based treatments for tendon injury, ligament injury, and osteoarthritis in dogs have been available to veterinarians in the United States since 2005. Over 3000 privately owned horses and dogs have been treated with autologous adipose-derived stem cells. The efficacy of these treatments has been shown in double-blind clinical trials for dogs with osteoarthritis of the hip and elbow and horses with tendon damage.[90][91]

Race horses are especially prone to injuries of the tendon and ligaments. Conventional therapies are very unsuccessful in returning the horse to full functioning potential. Natural healing, guided by the conventional treatments, leads to the formation of fibrous scar tissue that reduces flexibility and full joint movement. Traditional treatments prevented a large number of horses from returning to full activity and also have a high incidence of re-injury due to the stiff nature of the scarred tendon. Introduction of both bone marrow and adipose derived stem cells, along with natural mechanical stimulus promoted the regeneration of tendon tissue. The natural movement promoted the alignment of the new fibers and tendocytes with the natural alignment found in uninjured tendons. Stem cell treatment not only allowed more horses to return to full duty and also greatly reduced the re-injury rate over a three-year period.[64]

The use of embryonic stem cells has also been applied to tendon repair. The embryonic stem cells were shown to have a better survival rate in the tendon as well as better migrating capabilities to reach all areas of damaged tendon. The overall repair quality was also higher, with better tendon architecture and collagen formed. There was also no tumor formation seen during the three-month experimental period. Long-term studies need to be carried out to examine the long-term efficacy and risks associated with the use of embryonic stem cells.[64] Similar results have been found in small animals.[64]

Osteoarthritis is the main cause of joint pain both in animals and humans. Horses and dogs are most frequently affected by arthritis. Natural cartilage regeneration is very limited and no current drug therapies are curative, but rather look to reduce the symptoms associated with the degeneration. Different types of mesenchymal stem cells and other additives are still being researched to find the best type of cell and method for long-term treatment.[64]

Adipose-derived mesenchymal cells are currently the most often used because of the non-invasive harvesting. There has been a lot of success recently injecting mesenchymal stem cells directly into the joint. This is a recently developed, non-invasive technique developed for easier clinical use. Dogs receiving this treatment showed greater flexibility in their joints and less pain.[92]

Stem cells have successfully been used to ameliorate healing in the heart after myocardial infarction in dogs. Adipose and bone marrow derived stem cells were removed and induced to a cardiac cell fate before being injected into the heart. The heart was found to have improved contractility and a reduction in the damaged area four weeks after the stem cells were applied.[93]

A different trial is underway for a patch made of a porous substance onto which the stem cells are “seeded” in order to induce tissue regeneration in heart defects. Tissue was regenerated and the patch was well incorporated into the heart tissue. This is thought to be due, in part, to improved angiogenesis and reduction of inflammation. Although cardiomyocytes were produced from the mesenchymal stem cells, they did not appear to be contractile. Other treatments that induced a cardiac fate in the cells before transplanting had greater success at creating contractile heart tissue.[94]

Spinal cord injuries are one of the most common traumas brought into veterinary hospitals.[87] Spinal injuries occur in two ways after the trauma: the primary mechanical damage, and in secondary processes, like inflammation and scar formation, in the days following the trauma. These cells involved in the secondary damage response secrete factors that promote scar formation and inhibit cellular regeneration. Mesenchymal stem cells that are induced to a neural cell fate are loaded onto a porous scaffold and are then implanted at the site of injury. The cells and scaffold secrete factors that counteract those secreted by scar forming cells and promote neural regeneration. Eight weeks later, dogs treated with stem cells showed immense improvement over those treated with conventional therapies. Dogs treated with stem cells were able to occasionally support their own weight, which has not been seen in dogs undergoing conventional therapies.[95][96][97]

Treatments are also in clinical trials to repair and regenerate peripheral nerves. Peripheral nerves are more likely to be damaged, but the effects of the damage are not as widespread as seen in injuries to the spinal cord. Treatments are currently in clinical trials to repair severed nerves, with early success. Stem cells induced to a neural fate injected in to a severed nerve. Within four weeks, regeneration of previously damaged stem cells and completely formed nerve bundles were observed.[71]

Stem cells are also in clinical phases for treatment in ophthalmology. Hematopoietic stem cells have been used to treat corneal ulcers of different origin of several horses. These ulcers were resistant to conventional treatments available, but quickly responded positively to the stem cell treatment. Stem cells were also able to restore sight in one eye of a horse with retinal detachment, allowing the horse to return to daily activities.[72]

Pre-clinical models of Sjgrens syndrome[98][99] have culminated in allogeneic MSCs implanted around the lacrimal glands in KSC dogs that were refractory to current therapy. Significantly improved scores in ocular discharge, conjunctival hyperaemia, corneal changes and Schirmer tear tests (STT) were seen.[100]

In the late 1990s and early 2000s there was an initial wave of companies and clinics offering stem cell therapy to desperate people, often with extraordinary claims about what stem cells could do. Such companies and clinics included Advanced Cell Therapeutics, Stowe BioTherapy, Cells4Health run by Cornelis Kleinbloesem, the Beijing Xishan Institute for Neuroregeneration and Functional Recovery in Shijingshan run by Huang Hongyun, and EmCell in Kiev, Ukraine run by Alexandr Smikodub.[101][102] These clinics made strong claims about their outcomes, but rarely published their protocols or rigorous research showing that their therapies were safe and effective.[101]

By 2012 a second wave of companies and clinics had emerged, usually located in developing countries where medicine is less regulated and offering stem cell therapies on a medical tourism model.[102][103] Like the first wave companies and clinics, they have made similar strong claims and also have not published their protocols or rigorous research; Mexico, Thailand, and India have been centers of this activity,[102] as has South Africa.[103]

Continue reading here:

Stem-cell therapy – Wikipedia

Stem cell – Wikipedia

Stem cells are biological cells that can differentiate into other types of cells and can divide to produce more of the same type of stem cells. They are found in multicellular organisms.

In mammals, there are two broad types of stem cells: embryonic stem cells, which are isolated from the inner cell mass of blastocysts, and adult stem cells, which are found in various tissues. In adult organisms, stem cells and progenitor cells act as a repair system for the body, replenishing adult tissues. In a developing embryo, stem cells can differentiate into all the specialized cellsectoderm, endoderm and mesoderm (see induced pluripotent stem cells)but also maintain the normal turnover of regenerative organs, such as blood, skin, or intestinal tissues.

There are three known accessible sources of autologous adult stem cells in humans:

Stem cells can also be taken from umbilical cord blood just after birth. Of all stem cell types, autologous harvesting involves the least risk. By definition, autologous cells are obtained from one’s own body, just as one may bank his or her own blood for elective surgical procedures.

Adult stem cells are frequently used in various medical therapies (e.g., bone marrow transplantation). Stem cells can now be artificially grown and transformed (differentiated) into specialized cell types with characteristics consistent with cells of various tissues such as muscles or nerves. Embryonic cell lines and autologous embryonic stem cells generated through somatic cell nuclear transfer or dedifferentiation have also been proposed as promising candidates for future therapies.[1] Research into stem cells grew out of findings by Ernest A. McCulloch and James E. Till at the University of Toronto in the 1960s.[2][3]

The classical definition of a stem cell requires that it possesses two properties:

Two mechanisms exist to ensure that a stem cell population is maintained:

1. Obligatory asymmetric replication: a stem cell divides into one mother cell that is identical to the original stem cell, and another daughter cell that is differentiated.

When a stem cell self-renews it divides and does not disrupt the undifferentiated state. This self-renewal demands control of cell cycle as well as upkeep of multipotency or pluripotency, which all depends on the stem cell.[4]

2. Stochastic differentiation: when one stem cell develops into two differentiated daughter cells, another stem cell undergoes mitosis and produces two stem cells identical to the original.

Potency specifies the differentiation potential (the potential to differentiate into different cell types) of the stem cell.[5]

In practice, stem cells are identified by whether they can regenerate tissue. For example, the defining test for bone marrow or hematopoietic stem cells (HSCs) is the ability to transplant the cells and save an individual without HSCs. This demonstrates that the cells can produce new blood cells over a long term. It should also be possible to isolate stem cells from the transplanted individual, which can themselves be transplanted into another individual without HSCs, demonstrating that the stem cell was able to self-renew.

Properties of stem cells can be illustrated in vitro, using methods such as clonogenic assays, in which single cells are assessed for their ability to differentiate and self-renew.[8][9] Stem cells can also be isolated by their possession of a distinctive set of cell surface markers. However, in vitro culture conditions can alter the behavior of cells, making it unclear whether the cells shall behave in a similar manner in vivo. There is considerable debate as to whether some proposed adult cell populations are truly stem cells.[citation needed]

Embryonic stem cells (ESCs) are the cells of the inner cell mass of a blastocyst, an early-stage embryo.[10] Human embryos reach the blastocyst stage 45 days post fertilization, at which time they consist of 50150 cells. ESCs are pluripotent and give rise during development to all derivatives of the three primary germ layers: ectoderm, endoderm and mesoderm. In other words, they can develop into each of the more than 200 cell types of the adult body when given sufficient and necessary stimulation for a specific cell type. They do not contribute to the extra-embryonic membranes or the placenta.

During embryonic development these inner cell mass cells continuously divide and become more specialized. For example, a portion of the ectoderm in the dorsal part of the embryo specializes as ‘neurectoderm’, which will become the future central nervous system.[11] Later in development, neurulation causes the neurectoderm to form the neural tube. At the neural tube stage, the anterior portion undergoes encephalization to generate or ‘pattern’ the basic form of the brain. At this stage of development, the principal cell type of the CNS is considered a neural stem cell. These neural stem cells are pluripotent, as they can generate a large diversity of many different neuron types, each with unique gene expression, morphological, and functional characteristics. The process of generating neurons from stem cells is called neurogenesis. One prominent example of a neural stem cell is the radial glial cell, so named because it has a distinctive bipolar morphology with highly elongated processes spanning the thickness of the neural tube wall, and because historically it shared some glial characteristics, most notably the expression of glial fibrillary acidic protein (GFAP).[12][13] The radial glial cell is the primary neural stem cell of the developing vertebrate CNS, and its cell body resides in the ventricular zone, adjacent to the developing ventricular system. Neural stem cells are committed to the neuronal lineages (neurons, astrocytes, and oligodendrocytes), and thus their potency is restricted.[11]

Nearly all research to date has made use of mouse embryonic stem cells (mES) or human embryonic stem cells (hES) derived from the early inner cell mass. Both have the essential stem cell characteristics, yet they require very different environments in order to maintain an undifferentiated state. Mouse ES cells are grown on a layer of gelatin as an extracellular matrix (for support) and require the presence of leukemia inhibitory factor (LIF) in serum media. A drug cocktail containing inhibitors to GSK3B and the MAPK/ERK pathway, called 2i, has also been shown to maintain pluripotency in stem cell culture.[14] Human ESCs are grown on a feeder layer of mouse embryonic fibroblasts and require the presence of basic fibroblast growth factor (bFGF or FGF-2).[15] Without optimal culture conditions or genetic manipulation,[16] embryonic stem cells will rapidly differentiate.

A human embryonic stem cell is also defined by the expression of several transcription factors and cell surface proteins. The transcription factors Oct-4, Nanog, and Sox2 form the core regulatory network that ensures the suppression of genes that lead to differentiation and the maintenance of pluripotency.[17] The cell surface antigens most commonly used to identify hES cells are the glycolipids stage specific embryonic antigen 3 and 4 and the keratan sulfate antigens Tra-1-60 and Tra-1-81. By using human embryonic stem cells to produce specialized cells like nerve cells or heart cells in the lab, scientists can gain access to adult human cells without taking tissue from patients. They can then study these specialized adult cells in detail to try and catch complications of diseases, or to study cells reactions to potentially new drugs. The molecular definition of a stem cell includes many more proteins and continues to be a topic of research.[18]

There are currently no approved treatments using embryonic stem cells. The first human trial was approved by the US Food and Drug Administration in January 2009.[19] However, the human trial was not initiated until October 13, 2010 in Atlanta for spinal cord injury research. On November 14, 2011 the company conducting the trial (Geron Corporation) announced that it will discontinue further development of its stem cell programs.[20] ES cells, being pluripotent cells, require specific signals for correct differentiationif injected directly into another body, ES cells will differentiate into many different types of cells, causing a teratoma. Differentiating ES cells into usable cells while avoiding transplant rejection are just a few of the hurdles that embryonic stem cell researchers still face.[21] Due to ethical considerations, many nations currently have moratoria or limitations on either human ES cell research or the production of new human ES cell lines. Because of their combined abilities of unlimited expansion and pluripotency, embryonic stem cells remain a theoretically potential source for regenerative medicine and tissue replacement after injury or disease.[22]

Human embryonic stem cell colony on mouse embryonic fibroblast feeder layer

The primitive stem cells located in the organs of fetuses are referred to as fetal stem cells.[23]There are two types of fetal stem cells:

Adult stem cells, also called somatic (from Greek , “of the body”) stem cells, are stem cells which maintain and repair the tissue in which they are found.[25] They can be found in children, as well as adults.[26]

Pluripotent adult stem cells are rare and generally small in number, but they can be found in umbilical cord blood and other tissues.[27] Bone marrow is a rich source of adult stem cells,[28] which have been used in treating several conditions including liver cirrhosis,[29] chronic limb ischemia [30] and endstage heart failure.[31] The quantity of bone marrow stem cells declines with age and is greater in males than females during reproductive years.[32] Much adult stem cell research to date has aimed to characterize their potency and self-renewal capabilities.[33] DNA damage accumulates with age in both stem cells and the cells that comprise the stem cell environment. This accumulation is considered to be responsible, at least in part, for increasing stem cell dysfunction with aging (see DNA damage theory of aging).[34]

Most adult stem cells are lineage-restricted (multipotent) and are generally referred to by their tissue origin (mesenchymal stem cell, adipose-derived stem cell, endothelial stem cell, dental pulp stem cell, etc.).[35][36] Muse cells (multi-lineage differentiating stress enduring cells) are a recently discovered pluripotent stem cell type found in multiple adult tissues, including adipose, dermal fibroblasts, and bone marrow. While rare, muse cells are identifiable by their expression of SSEA-3, a marker for undifferentiated stem cells, and general mesenchymal stem cells markers such as CD105. When subjected to single cell suspension culture, the cells will generate clusters that are similar to embryoid bodies in morphology as well as gene expression, including canonical pluripotency markers Oct4, Sox2, and Nanog.[37]

Adult stem cell treatments have been successfully used for many years to treat leukemia and related bone/blood cancers through bone marrow transplants.[38] Adult stem cells are also used in veterinary medicine to treat tendon and ligament injuries in horses.[39]

The use of adult stem cells in research and therapy is not as controversial as the use of embryonic stem cells, because the production of adult stem cells does not require the destruction of an embryo. Additionally, in instances where adult stem cells are obtained from the intended recipient (an autograft), the risk of rejection is essentially non-existent. Consequently, more US government funding is being provided for adult stem cell research.[40]

Multipotent stem cells are also found in amniotic fluid. These stem cells are very active, expand extensively without feeders and are not tumorigenic. Amniotic stem cells are multipotent and can differentiate in cells of adipogenic, osteogenic, myogenic, endothelial, hepatic and also neuronal lines.[41]Amniotic stem cells are a topic of active research.

Use of stem cells from amniotic fluid overcomes the ethical objections to using human embryos as a source of cells. Roman Catholic teaching forbids the use of embryonic stem cells in experimentation; accordingly, the Vatican newspaper “Osservatore Romano” called amniotic stem cells “the future of medicine”.[42]

It is possible to collect amniotic stem cells for donors or for autologuous use: the first US amniotic stem cells bank [43][44] was opened in 2009 in Medford, MA, by Biocell Center Corporation[45][46][47] and collaborates with various hospitals and universities all over the world.[48]

Adult stem cells have limitations with their potency; unlike embryonic stem cells (ESCs), they are not able to differentiate into cells from all three germ layers. As such, they are deemed multipotent.

However, reprogramming allows for the creation of pluripotent cells, induced pluripotent stem cells (iPSCs), from adult cells. These are not adult stem cells, but adult cells (e.g. epithelial cells) reprogrammed to give rise to cells with pluripotent capabilities. Using genetic reprogramming with protein transcription factors, pluripotent stem cells with ESC-like capabilities have been derived.[49][50][51] The first demonstration of induced pluripotent stem cells was conducted by Shinya Yamanaka and his colleagues at Kyoto University.[52] They used the transcription factors Oct3/4, Sox2, c-Myc, and Klf4 to reprogram mouse fibroblast cells into pluripotent cells.[49][53] Subsequent work used these factors to induce pluripotency in human fibroblast cells.[54] Junying Yu, James Thomson, and their colleagues at the University of WisconsinMadison used a different set of factors, Oct4, Sox2, Nanog and Lin28, and carried out their experiments using cells from human foreskin.[49][55] However, they were able to replicate Yamanaka’s finding that inducing pluripotency in human cells was possible.

Induced pluripotent stem cells differ from embryonic stem cells. They share many similar properties, such as pluripotency and differentiation potential, the expression of pluripotency genes, epigenetic patterns, embryoid body and teratoma formation, and viable chimera formation,[52][53] but there are many differences within these properties. The chromatin of iPSCs appears to be more “closed” or methylated than that of ESCs.[52][53] Similarly, the gene expression pattern between ESCs and iPSCs, or even iPSCs sourced from different origins.[52] There are thus questions about the “completeness” of reprogramming and the somatic memory of induced pluripotent stem cells. Despite this, inducing adult cells to be pluripotent appears to be viable.

As a result of the success of these experiments, Ian Wilmut, who helped create the first cloned animal Dolly the Sheep, has announced that he will abandon somatic cell nuclear transfer as an avenue of research.[56]

Furthermore, induced pluripotent stem cells provide several therapeutic advantages. Like ESCs, they are pluripotent. They thus have great differentiation potential; theoretically, they could produce any cell within the human body (if reprogramming to pluripotency was “complete”).[52] Moreover, unlike ESCs, they potentially could allow doctors to create a pluripotent stem cell line for each individual patient.[57] Frozen blood samples can be used as a valuable source of induced pluripotent stem cells.[58] Patient specific stem cells allow for the screening for side effects before drug treatment, as well as the reduced risk of transplantation rejection.[57] Despite their current limited use therapeutically, iPSCs hold create potential for future use in medical treatment and research.

To ensure self-renewal, stem cells undergo two types of cell division (see Stem cell division and differentiation diagram). Symmetric division gives rise to two identical daughter cells both endowed with stem cell properties. Asymmetric division, on the other hand, produces only one stem cell and a progenitor cell with limited self-renewal potential. Progenitors can go through several rounds of cell division before terminally differentiating into a mature cell. It is possible that the molecular distinction between symmetric and asymmetric divisions lies in differential segregation of cell membrane proteins (such as receptors) between the daughter cells.[59]

An alternative theory is that stem cells remain undifferentiated due to environmental cues in their particular niche. Stem cells differentiate when they leave that niche or no longer receive those signals. Studies in Drosophila germarium have identified the signals decapentaplegic and adherens junctions that prevent germarium stem cells from differentiating.[60][61]

Stem cell therapy is the use of stem cells to treat or prevent a disease or condition. Bone marrow transplant is a form of stem cell therapy that has been used for many years without controversy.[62][63]

Stem cell treatments may lower symptoms of the disease or condition that is being treated. The lowering of symptoms may allow patients to reduce the drug intake of the disease or condition. Stem cell treatment may also provide knowledge for society to further stem cell understanding and future treatments.[64]

Stem cell treatments may require immunosuppression because of a requirement for radiation before the transplant to remove the person’s previous cells, or because the patient’s immune system may target the stem cells. One approach to avoid the second possibility is to use stem cells from the same patient who is being treated.

Pluripotency in certain stem cells could also make it difficult to obtain a specific cell type. It is also difficult to obtain the exact cell type needed, because not all cells in a population differentiate uniformly. Undifferentiated cells can create tissues other than desired types.[65]

Some stem cells form tumors after transplantation;[66] pluripotency is linked to tumor formation especially in embryonic stem cells, fetal proper stem cells, induced pluripotent stem cells. Fetal proper stem cells form tumors despite multipotency.[67]

Some of the fundamental patents covering human embryonic stem cells are owned by the Wisconsin Alumni Research Foundation (WARF) they are patents 5,843,780, 6,200,806, and 7,029,913 invented by James A. Thomson. WARF does not enforce these patents against academic scientists, but does enforce them against companies.[68]

In 2006, a request for the US Patent and Trademark Office (USPTO) to re-examine the three patents was filed by the Public Patent Foundation on behalf of its client, the non-profit patent-watchdog group Consumer Watchdog (formerly the Foundation for Taxpayer and Consumer Rights).[68] In the re-examination process, which involves several rounds of discussion between the USPTO and the parties, the USPTO initially agreed with Consumer Watchdog and rejected all the claims in all three patents,[69] however in response, WARF amended the claims of all three patents to make them more narrow, and in 2008 the USPTO found the amended claims in all three patents to be patentable. The decision on one of the patents (7,029,913) was appealable, while the decisions on the other two were not.[70][71] Consumer Watchdog appealed the granting of the ‘913 patent to the USPTO’s Board of Patent Appeals and Interferences (BPAI) which granted the appeal, and in 2010 the BPAI decided that the amended claims of the ‘913 patent were not patentable.[72] However, WARF was able to re-open prosecution of the case and did so, amending the claims of the ‘913 patent again to make them more narrow, and in January 2013 the amended claims were allowed.[73]

In July 2013, Consumer Watchdog announced that it would appeal the decision to allow the claims of the ‘913 patent to the US Court of Appeals for the Federal Circuit (CAFC), the federal appeals court that hears patent cases.[74] At a hearing in December 2013, the CAFC raised the question of whether Consumer Watchdog had legal standing to appeal; the case could not proceed until that issue was resolved.[75]

Diseases and conditions where stem cell treatment is being investigated include:

Research is underway to develop various sources for stem cells, and to apply stem cell treatments for neurodegenerative diseases and conditions, diabetes, heart disease, and other conditions.[91] Research is also underway in generating organoids using stem cells, which would allow for further understanding of human development, organogenesis, and modeling of human diseases.[92]

In more recent years, with the ability of scientists to isolate and culture embryonic stem cells, and with scientists’ growing ability to create stem cells using somatic cell nuclear transfer and techniques to create induced pluripotent stem cells, controversy has crept in, both related to abortion politics and to human cloning.

Hepatotoxicity and drug-induced liver injury account for a substantial number of failures of new drugs in development and market withdrawal, highlighting the need for screening assays such as stem cell-derived hepatocyte-like cells, that are capable of detecting toxicity early in the drug development process.[93]

See the original post:

Stem cell – Wikipedia

NSI Stem Cell | Stem Cell Therapy & Treatment Clinics In …

The process begins first with a physical exam and in-depth patient history. We do this to give you the best proper diagnosis and therapy. If additional information is needed, we will conduct the necessary imaging or laboratory tests. We will then discuss patient desires and expected outcomes as well as educate on his/her condition and all possible therapy options.

The Stem Cell procedure is minimally invasive, gathering a sample of tissue from the patient. These cells remain sterile and after adult stem cells are extracted, they will be re-administered back into the patient. This is done by one of the three methods: Intravenous, Intrathecal, or Localized.

Our Stem Cell procedure is safe and there are no concerns about cell rejection or disease transmission because the tissue extracted remains in a sterile environment and comes from your own body. In addition, all aspects of the procedure are performed in-house on an outpatient basis.

Go here to see the original:

NSI Stem Cell | Stem Cell Therapy & Treatment Clinics In …

Stem Cell Malaysia | Stem Cell Anti Ageing Therapy

When stem cells are diminished in your body, the number of dying and old cells continues to increase. Due to this, stem cell therapy is used to increase the number of stem cells in your body. This is an excellent method to fight various effects and signs of aging.

If you wish to bring back the healthy and refreshing years of your life,Cell Malaysia recommends the age-reverse procedure practiced in one of worlds most advanced clinic.

Follow this link:

Stem Cell Malaysia | Stem Cell Anti Ageing Therapy

Welcome to AynRand.org | AynRand.org

AynRand.org is the official website of the Ayn Rand Institute (ARI), the source for information on the life, writings and work of novelist-philosopher Ayn Rand.

Headquartered in Irvine, California, ARI offers educational experiences based on Ayn Rands books and ideas for a variety of audiences, including students, educators, policymakers and lifelong learners. ARI also engages in research and advocacy efforts, applying Rands ideas to current issues and seeking to promote her philosophical principles of reason, rational self-interest and laissez-faire capitalism.

ARI is composed of a dedicated Board of Directors and an energetic staff of more than 55 people. We invite you to explore how Ayn Rand viewed the world and to consider the distinctive insights offered by ARIs thought leaders today.

See the original post here:

Welcome to AynRand.org | AynRand.org

Who Is Ayn Rand? – The Objective Standard

Ayn Rand (19051982) was an American novelist and philosopher, and the creator of Objectivism, which she called a philosophy for living on earth.

Rands most widely read novels are The Fountainhead, a story about an independent and uncompromising architect; and Atlas Shrugged, a story about the role of the mind in human life and about what happens to the world when the thinkers and producers mysteriously disappear. Her most popular nonfiction books are The Virtue of Selfishness, a series of essays about the foundations and principles of the morality of self-interest; and Capitalism: The Unknown Ideal, a series of essays about what capitalism is and why it is the only moral social system.

Rand was born in Russia, where she attended grade school and university; studied history, philosophy, and screenwriting; and witnessed the Bolshevik Revolution and the birth of the Union of Soviet Socialist Republics. In 1925, she left the burgeoning communist state, telling Soviet authorities she was going for a brief visit with relatives in America, and never returned.

She soon made her way to Hollywood, where she worked as a screenwriter, married actor Frank OConnor, and wrote her first novel, We The Living. She then moved to New York City, where she wrote Anthem (a novelette), The Fountainhead, Atlas Shrugged, numerous articles and essays, and several nonfiction books in which she defined and elaborated the principles of Objectivism.

Rands staunch advocacy of reason (as against faith and whim), self-interest (as against self-sacrifice), individualism and individual rights (as against collectivism and group rights), and capitalism (as against all forms of statism) make her both the most controversial and most important philosopher of the 20th century.

Describing Objectivism, Rand wrote: My philosophy, in essence, is the concept of man as a heroic being, with his own happiness as the moral purpose of his life, with productive achievement as his noblest activity, and reason as his only absolute.

For a good biography of Rand, see Jeffery Brittings Ayn Rand or Scott McConnells 100 Voices: An Oral History of Ayn Rand. For a brief presentation of the principles of Objectivism, see What is Objectivism? For the application of these principles to cultural and political issues of the day, subscribe to The Objective Standard, the preeminent source for commentary from an Objectivist perspective.

Continue reading here:

Who Is Ayn Rand? – The Objective Standard

Welcome to The Ayn Rand Institute | The Ayn Rand Institute

Ayn Rand (1905 1982) was a novelist and philosopher. She is best known for her novels Atlas Shrugged and The Fountainhead, and for the revolutionary philosophy she originated, Objectivism.

Ayn Rands philosophy for living on earth has changed the lives of millions and continues to influence American culture and politics. The Ayn Rand Institute is dedicated to advancing her principles of reason, rational self-interest and laissez-faire capitalism.

Ready to learn more about Ayn Rand and Objectivism?

Read more from the original source:

Welcome to The Ayn Rand Institute | The Ayn Rand Institute


...1020...2829303132...405060...