Stem cell combination therapy improves traumatic brain injury outcomes

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Traumatic brain injuries (TBI), sustained by close to 2 million Americans annually, including military personnel, are debilitating and devastating for patients and their families. Regardless of severity, those with TBI can suffer a range of motor, behavioral, intellectual and cognitive disabilities over the short or long term. Sadly, clinical treatments for TBI are few and largely ineffective.

In an effort to find an effective therapy, neuroscientists at the Center of Excellence for Aging and Brain Repair, Department of Neurosurgery in the USF Health Morsani College of Medicine, University of South Florida, have conducted several preclinical studies aimed at finding combination therapies to improve TBI outcomes.

In their study of several different therapies -- alone and in combination -- applied to laboratory rats modeled with TBI, USF researchers found that a combination of human umbilical cord blood cells (hUBCs) and granulocyte colony stimulating factor (G-CSF), a growth factor, was more therapeutic than either administered alone, or each with saline, or saline alone.

The study appeared in a recent issue of PLoS ONE.

"Chronic TBI is typically associated with major secondary molecular injuries, including chronic neuroinflammation, which not only contribute to the death of neuronal cells in the central nervous system, but also impede any natural repair mechanism," said study lead author Cesar V. Borlongan, PhD, professor of neurosurgery and director of USF's Center of Excellence for Aging and Brain Repair. "In our study, we used hUBCs and G-CSF alone and in combination. In previous studies, hUBCs have been shown to suppress inflammation, and G-CSF is currently being investigated as a potential therapeutic agent for patients with stroke or Alzheimer's disease."

Their stand-alone effects have a therapeutic potential for TBI, based on results from previous studies. For example, G-CSF has shown an ability to mobilize stem cells from bone marrow and then infiltrate injured tissues, promoting self-repair of neural cells, while hUBCs have been shown to suppress inflammation and promote cell growth.

The involvement of the immune system in the central nervous system to either stimulate repair or enhance molecular damage has been recognized as key to the progression of many neurological disorders, including TBI, as well as in neurodegenerative diseases such as Parkinson's disease, multiple sclerosis and some autoimmune diseases, the researchers report. Increased expression of MHCII positive cells -- cell members that secrete a family of molecules mediating interactions between the immune system's white blood cells -- has been directly linked to neurodegeneration and cognitive decline in TBI.

"Our results showed that the combined therapy of hUBCs and G-CSF significantly reduced the TBI-induced loss of neuronal cells in the hippocampus," said Borlongan. "Therapy with hUBCs and G-CSF alone or in combination produced beneficial results in animals with experimental TBI. G-CSF alone produced only short-lived benefits, while hUBCs alone afforded more robust and stable improvements. However, their combination offered the best motor improvement in the laboratory animals."

"This outcome may indicate that the stem cells had more widespread biological action than the drug therapy," said Paul R. Sanberg, distinguished professor at USF and principal investigator of the Department of Defense funded project. "Regardless, their combination had an apparent synergistic effect and resulted in the most effective amelioration of TBI-induced behavioral deficits."

The researchers concluded that additional studies of this combination therapy are warranted in order to better understand their modes of action. While this research focused on motor improvements, they suggested that future combination therapy research should also include analysis of cognitive improvement in the laboratory animals modeled with TBI.

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Stem cell combination therapy improves traumatic brain injury outcomes

USF study finds stem cell combination therapy improves traumatic brain injury outcomes

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PUBLIC RELEASE DATE:

20-Mar-2014

Contact: Anne DeLotto Baier abaier@health.usf.edu 813-974-3303 University of South Florida (USF Innovation)

Tampa, FL (Mar. 20, 2014) Traumatic brain injuries (TBI), sustained by close to 2 million Americans annually, including military personnel, are debilitating and devastating for patients and their families. Regardless of severity, those with TBI can suffer a range of motor, behavioral, intellectual and cognitive disabilities over the short or long term. Sadly, clinical treatments for TBI are few and largely ineffective.

In an effort to find an effective therapy, neuroscientists at the Center of Excellence for Aging and Brain Repair, Department of Neurosurgery in the USF Health Morsani College of Medicine, University of South Florida, have conducted several preclinical studies aimed at finding combination therapies to improve TBI outcomes.

In their study of several different therapiesalone and in combinationapplied to laboratory rats modeled with TBI, USF researchers found that a combination of human umbilical cord blood cells (hUBCs) and granulocyte colony stimulating factor (G-CSF), a growth factor, was more therapeutic than either administered alone, or each with saline, or saline alone.

The study appeared in a recent issue of PLoS ONE.

"Chronic TBI is typically associated with major secondary molecular injuries, including chronic neuroinflammation, which not only contribute to the death of neuronal cells in the central nervous system, but also impede any natural repair mechanism," said study lead author Cesar V. Borlongan, PhD, professor of neurosurgery and director of USF's Center of Excellence for Aging and Brain Repair. "In our study, we used hUBCs and G-CSF alone and in combination. In previous studies, hUBCs have been shown to suppress inflammation, and G-CSF is currently being investigated as a potential therapeutic agent for patients with stroke or Alzheimer's disease."

Their stand-alone effects have a therapeutic potential for TBI, based on results from previous studies. For example, G-CSF has shown an ability to mobilize stem cells from bone marrow and then infiltrate injured tissues, promoting self-repair of neural cells, while hUBCs have been shown to suppress inflammation and promote cell growth.

The involvement of the immune system in the central nervous system to either stimulate repair or enhance molecular damage has been recognized as key to the progression of many neurological disorders, including TBI, as well as in neurodegenerative diseases such as Parkinson's disease, multiple sclerosis and some autoimmune diseases, the researchers report. Increased expression of MHCII positive cellscell members that secrete a family of molecules mediating interactions between the immune system's white blood cellshas been directly linked to neurodegeneration and cognitive decline in TBI.

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USF study finds stem cell combination therapy improves traumatic brain injury outcomes

Stem cells created from a drop of blood: DIY finger-prick technique opens door for extensive stem cell banking

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Scientists at A*STAR's Institute of Molecular and Cell Biology (IMCB) have developed a method to generate human induced pluripotent stem cells (hiPSCs) from a single drop of finger-pricked blood. The method also enables donors to collect their own blood samples, which they can then send to a laboratory for further processing. The easy access to blood samples using the new technique could potentially boost the recruitment of greater numbers and diversities of donors, and could lead to the establishment of large-scale hiPSC banks.

By genetic reprogramming, matured human cells, usually blood cells, can be transformed into hiPSCs. As hiPSCs exhibit properties remarkably similar to human embryonic stem cells, they are invaluable resources for basic research, drug discovery and cell therapy. In countries like Japan, USA and UK, a number of hiPSC bank initiatives have sprung up to make hiPSCs available for stem cell research and medical studies.

Current sample collection for reprogramming into hiPSCs include invasive measures such as collecting cells from the bone marrow or skin, which may put off many potential donors. Although hiPSCs may also be generated from blood cells, large quantities of blood are usually required. In the paper published online on the Stem Cell Translational Medicine journal, scientists at IMCB showed for the first time that single-drop volumes of blood are sufficient for reprogramming into hiPSCs. The finger-prick technique is the world's first to use only a drop of finger-pricked blood to yield hiPSCs with high efficiency. A patent has been filed for the innovation.

The accessibility of the new technique is further enhanced with a DIY sample collection approach. Donors may collect their own finger-pricked blood, which they can then store and send it to a laboratory for reprogramming. The blood sample remains stable for 48 hours and can be expanded for 12 days in culture, which therefore extends the finger-prick technique to a wide range of geographical regions for recruitment of donors with varied ethnicities, genotypes and diseases.

By integrating it with the hiPSC bank initiatives, the finger-prick technique paves the way for establishing diverse and fully characterised hiPSC banking for stem cell research. The potential access to a wide range of hiPSCs could also replace the use of embryonic stem cells, which are less accessible. It could also facilitate the set-up of a small hiPSC bank in Singapore to study targeted local diseases.

Dr Loh Yuin Han Jonathan, Principal Investigator at IMCB and lead scientist for the finger-prick hiPSC technique, said, "It all began when we wondered if we could reduce the volume of blood used for reprogramming. We then tested if donors could collect their own blood sample in a normal room environment and store it. Our finger-prick technique, in fact, utilised less than a drop of finger-pricked blood. The remaining blood could even be used for DNA sequencing and other blood tests."

Dr Stuart Alexander Cook, Senior Consultant at the National Heart Centre Singapore and co-author of the paper, said "We were able to differentiate the hiPSCs reprogrammed from Jonathan's finger-prick technique, into functional heart cells. This is a well-designed, applicable technique that can unlock unrealized potential of biobanks around the world for hiPSC studies at a scale that was previously not possible."

Prof Hong Wanjin, Executive Director at IMCB, said "Research on hiPSCs is now highly sought-after, given its potential to be used as a model for studying human diseases and for regenerative medicine. Translational research and technology innovations are constantly encouraged at IMCB and this new technique is very timely. We hope to eventually help the scientific community gain greater accessibility to hiPSCs for stem cell research through this innovation."

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The above story is based on materials provided by A*STAR. Note: Materials may be edited for content and length.

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Stem cells created from a drop of blood: DIY finger-prick technique opens door for extensive stem cell banking

In the lab: Researchers uncovering clues to lung transplants and more

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A variety of research studies are underway at area medical schools and hospitals, from figuring out why lung transplants arent as successful as other organ transplants to whether stem cell therapy can help avoid amputations.

Using drugs to broadly suppress the immune system helps the body accept organ transplants of hearts, livers and kidneys. But not so with lung transplants, new research at Washington University School of Medicine suggests.

In what researchers call a surprising discovery, newly transplanted lungs in mice were more likely to be rejected if key immune cells called memory T cells were missing. Typically, memory T cells are knocked down with immunosuppressive drugs.

Memory T cells patrol the lungs for invaders from the environment such as viruses and bacteria. When researchers infused memory T cells into mice with lung transplants, the cells released signals that encouraged the immune system to accept the lung.

The research may help partly explain why lung transplants are not as successful as other organ transplants. Five years after lung transplants, only half are still functioning, figures show.

Researchers want to discover how to target immunosuppression in lung transplants in a way that would help memory T cells thrive while eliminating other T cells that are harmful.

Also at Washington U., researchers have found that a follow-up surgery after a stroke to clear fatty deposits from the neck should be delayed if the patient was recently treated with the clot-busting drug tPA.

After a stroke, physicians scan two large blood vessels in the neck, which provide much of brains blood supply. If one is more than 50 percent blocked with plaque, doctors commonly recommend surgical removal of the plaque called carotid endarterectomy a few days after the stroke to help reduce the chance a fragment will break free and cause another stroke.

Analyzing outcomes of 142 patients, researchers found those who received the surgery a few days after being treated with tPA were at higher risk for bleeding complications in the brain.

It may be that tPA caused microhemorrhages in the brain that surgery could worsen without allowing time for the blood vessels to heal; or tPA could be activating a molecular chain reaction that temporarily increases the risk of bleeding in the brain.

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In the lab: Researchers uncovering clues to lung transplants and more

Spirituality permeates Vemulawada

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The celestial wedding of Lord Siva with Goddess Parvati was held with religious fervour and gaiety at Sri Raja Rajeshwara Swamy Devasthanam in Vemulawada of Karimnagar district on Wednesday.

As part of the ritual, the temple priests performed ekadasa rudrabhishekam in the morning. Later, after the dwajarohan programme, the temple authorities conducted the edurukollo (receiving of groom) and after that the celestial wedding of Siva and Parvati was performed by the priests at 10.30 a.m. amid chanting of Vedic hymns. Temple EO Krishnaji Rao, the trust board members have acted as the elders of the marriage. In the evening, the Peddaseva (procession of deities) was conducted after the traditional homam. On March 22, a procession of the Trishul (trident) would be held and an abhishekam will be performed to the trishul at the holy tank. As part of the celebrations, the temple was illuminated and decorated with flowers. Devotees also arrived in large numbers to witness the celestial wedding. The Shiva Parvathulu also attended in large numbers to watch the celestial wedding and showered presideing deities with thalambralu. Arrangements for distribution of prasadam and anna danam were also made.

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Spirituality permeates Vemulawada

N.L. woman says family, spirituality helped her cope with ovarian cancer

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Published on March 20, 2014

ST. JOHN'S (TC Media) One of the first things Alice Gibbons did before starting chemotherapy in October was go see a hairdresser.

TC Media photo

Alice Gibbons ponders her battle with ovarian cancer during an interview in her St. Johns, N.L. apartment the day after receiving her last chemo treatment.

Diagnosed last summer with ovarian cancer, the 48-year-old said she wasnt waiting for the treatment to take her hair.

It didnt bother me, Gibbons said of having her head shaved.

I was told it hurts more if you lose it during treatments, so I went to the salon the owner is a breast cancer survivor and they took me to a special room and cut my hair short and then shaved it, she said, rubbing her hand over her porcelain-textured scalp.

During a recent interview about her experience fighting cancer the chemotherapy as well as the health care she received Gibbons is upbeat and bubbly as she talks about her eyelashes falling out, the needles and the pain.

The whole ordeal, she said, has left her with a profound sense of faith.

I was never a spiritual person, but since all of this I have developed a level of acceptance and spirituality that I never had before. I think that is what got me through it, she said, sipping a cup of orange juice as one of her three small cats snakes around her legs.

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Google's Project Tango headed to International Space Station

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Googles Project Tango, the prototype smartphone packed with sensors so it can learn and sense the world around it, is heading to the International Space Station.

Two of the Tango phones are due to be launched to the ISS on the upcoming Orbital 2 mission, which is scheduled to launch in May and take supplies to the station. The phones will be used as part of a NASA project thats developing robots that could one day fly around the inside or outside of the space station, or even be used in NASAs planned mission to land on an asteroid.

Work on the robots is already going on at NASAs Ames Research Center in Silicon Valley, and this week the space agency let a small group of reporters visit its lab and see some of the research.

Three Spheres satellites float inside the International Space Station.

The phones, which are being supplied to a limited number of developers at present, were unveiled by Google a month ago. They include several cameras and infrared range-finding so the phone can build up a three-dimensional model of its surroundingsa significant difference from current handsets that can see only a two-dimensional world through a single camera.

Google has already shown the phones being used to build up a detailed map of the interior of a home or office, but NASA has much bigger plans. At Ames, which is just minutes from Googles Mountain View headquarters, researchers have attached a Tango handset to a robot development platform called a Sphere.

Technically an 18-sided polyhedron, each Sphere is about the size of a soccer ball and self-powered. They can free-fly around the inside of the ISS thanks to carbon dioxide-powered thrusters, said Chris Provencher, Smart Spheres project manager at NASA.

The Spheres have already been used in developing autonomous equipment. The space agency conducted a Spheres test with a Nexus S smartphone as part of Shuttle mission STS-135 in 2011, but the Tango phones promise more capabilities.

We are researching how effective Project Tangos vision-based navigation capabilities are for performing localization and navigation of a mobile free flyer on ISS, said Andres Martinez, Spheres Manager at NASA.

Specifically, we are researching how well the 3-D modeling and visual odometry can be used to let the [Spheres] free flyer learn its environment and maneuver through it based on what it sees, said Martinez. This is in contrast to the current Spheres localization system, which relies on fixed sensors in the environment to help the Spheres track its position.

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Amazing Anatomy Of The James Webb Space Telescope Mirrors

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Image Caption: Technicians and scientists check out one of the Webb telescope's first two flight mirrors in the clean room at NASA's Goddard Space Flight Center in Greenbelt, Md. Credit: NASA/Chris Gunn

Rob Gutro, NASA

When you think of a mirror, there really isnt that much needed to describe it, but when you look at a mirror that will fly aboard NASAs next-generation James Webb Space Telescope, theres a lot to the anatomy of a mirror.

NASAs Webb telescope includes a primary, secondary and tertiary mirror. Although the relatively small secondary and tertiary mirrors are unique, its the expansive primary mirror that has the most complicated anatomy with a number of components operating together to make the telescope work.

The mirrors were built by Ball Aerospace & Technologies Corp., Boulder, Colo. Ball is the principal subcontractor to Northrop Grumman for the optical technology and lightweight mirror system. Ball Aerospace also developed the secondary mirror, tertiary mirror and fine-steering mirror.

The raw power of any telescope is determined by the size of its main optic the bigger the first or primary optic, the betterand in the case of large telescopes, the optic is a mirror. Webbs primary mirror measures 6.5 meters (21 feet, 4 inches) across, and although thats respectable by ground-based telescope standards, it is absolutely huge for a space telescope. A mirror this large and in space is needed to capture the light from the most distant galaxies and stars in the universe, but it would too big to launch into space if it were one single piece, so thats why Webbs is composed of 18 smaller lightweight segments that can be folded up to fit into the nosecone of a rocket. Each of Webbs 18 hexagonal-shaped primary mirror segments measures just over 1.3 meters (4.2 feet) across, and weighs approximately 40 kilograms (88 pounds). All of the 18 primary mirror segment assemblies that will fly aboard NASAs James Webb Space Telescope have already arrived at NASAs Goddard Space Flight Center in Greenbelt, Md.

Each of the 18 mirror segments is not just a mirror but is a complex assembly of technologies that allows all of them to work together as one. Each mirror has an anatomy of many parts, from the reflective gold-coated Beryllium substrate or layer, down to a Beryllium structure of whiffles and a Delta frame, plus precision actuators to position and shape the mirror, mounted on Backplane Interface Flexures.

The complexity of the mirror assemblies comes from the fact that they are designed to be very lightweight, work at cryogenic temperatures below -400F, survive launch vibration and forces, be align-able on-orbit via actuators, and then stay aligned for up to two weeks as though they are a single large mirror, said Lee Feinberg, NASA Optical Telescope Element Manager for the James Webb Space Telescope at the Goddard Space Flight Center in Greenbelt, Maryland.

Beryllium Mirror Substrate (Smooth mirror surface)

The Beryllium Mirror Substrate is the part of each mirror segment that acts as a mirror in the classic sense. Each substrate is nearly 2 inches thick with a highly-polished and exquisitely smooth front reflective side and a back side that is precision machined into a sort of egg crate-looking structure to make it lighter weight than it would be if solid. The reflective surface is polished to an average roughness of only 20 nanometers (i.e., 20 billionths of a meter) and coated with a microscopically thin layer of pure gold to maximize its ability to reflect infrared light. Beryllium is the material of choice because is it extremely stiff and lightweight, and it behaves very stably and predictably at Webbs extremely cold operating temperatures.

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Amazing Anatomy Of The James Webb Space Telescope Mirrors