Isolation and killing of candidate CML stem cells by antibody targeting

Isolation and killing of candidate chronic myeloid leukemia stem cells by antibody targeting of IL-1 receptor accessory protein by Marcus Järås and 10 co-authors, including Thoas Fioretos, Proc Natl Acad Sci USA 2010(Aug 30). OA article. [Epub ahead of print][PubMed citation]. Abstract:

Chronic myeloid leukemia (CML) is genetically characterized by the Philadelphia (Ph) chromosome, formed through a reciprocal translocation between chromosomes 9 and 22 and giving rise to the constitutively active tyrosine kinase P210 BCR/ABL1. Therapeutic strategies aiming for a cure of CML will require full eradication of Ph chromosome-positive (Ph(+)) CML stem cells. Here we used gene-expression profiling to identify IL-1 receptor accessory protein (IL1RAP) as up-regulated in CML CD34(+) cells and also in cord blood CD34(+) cells as a consequence of retroviral BCR/ABL1 expression. To test whether IL1RAP expression distinguishes normal (Ph(-)) and leukemic (Ph(+)) cells within the CML CD34(+)CD38(-) cell compartment, we established a unique protocol for conducting FISH on small numbers of sorted cells. By using this method, we sorted cells directly into drops on slides to investigate their Ph-chromosome status. Interestingly, we found that the CML CD34(+)CD38(-)IL1RAP(+) cells were Ph(+), whereas CML CD34(+)CD38(-)IL1RAP(-) cells were almost exclusively Ph(-). By performing long-term culture-initiating cell assays on the two cell populations, we found that Ph(+) and Ph(-) candidate CML stem cells could be prospectively separated. In addition, by generating an anti-IL1RAP antibody, we provide proof of concept that IL1RAP can be used as a target on CML CD34(+)CD38(-) cells to induce antibody-dependent cell-mediated cytotoxicity. This study thus identifies IL1RAP as a unique cell surface biomarker distinguishing Ph(+) from Ph(-) candidate CML stem cells and opens up a previously unexplored avenue for therapy of CML.

On the low frequency of tumor-initiating cells

Tumor-Initiating Cells Are Rare in Many Human Tumors by Kota Ishizawa and 16 co-authors, including Benjamin G Neel and William Matsui, Cell Stem Cell 2010(Sep 3); 7(3): 279-282. [FriendFeed entry][PubMed citation]. Abstract:

Tumor-initiating cells (TICs) are defined by their ability to form tumors after xenotransplantation in immunodeficient mice and appear to be relatively rare in most human cancers. Recent data in melanoma indicate that the frequency of TICs increases dramatically via more permissive xenotransplantation conditions, raising the possibility that the true frequency of TICs has been greatly underestimated in most human tumors. We compared the growth of human pancreatic, non-small cell lung, and head and neck carcinomas in NOD/SCID and NSG mice. Although TIC frequency was detected up to 10-fold higher in NSG mice, it remained low (<1 in 2500 cells) in all cases. Moreover, aldehyde dehydrogenase-positive (ALDH(+)) and CD44(+)CD24(+) cells, phenotypically distinct cells enriched in TICs, were equally tumorigenic in NOD/SCID and NSG mice. Our findings demonstrate that TICs are rare in these cancers and that the identification of TICs and their frequency in other human malignancies should be validated via primary tumors and highly permissive xenotransplantation conditions.

Some breast cancer tumors may not originate from stem cells?

Surprise breast cancer source by Jennifer Welsh,TheScientist.com, September 2, 2010. First paragraph:

Some breast cancer tumors may not originate from stem cells as previously believed, according to a study published in the September 3rd issue of Cell Stem Cell. The discovery is an important step in the development of treatments for these cancers.

This news story is based on the publication: BRCA1 Basal-like Breast Cancers Originate from Luminal Epithelial Progenitors and Not from Basal Stem Cells by Gemma Molyneux and 11 co-authors, including Matthew J Smalley, Cell Stem Cell 2010(Sep 3); 7(3): 403-417. OA article [Full text] [PubMed citation].

A commentary: Cancer Cell of Origin: Spotlight on Luminal Progenitors by Christine L Chaffer and Robert A Weinberg, Cell Stem Cell 2010(Sep 3); 7(3): 271-272. [PubMed citation].

Selective targeting of neuroblastoma tumour-initiating cells

Selective targeting of neuroblastoma tumour-initiating cells by compounds identified in stem cell-based small molecule screens by Kristen M Smith and 16 co-authors, including David R Kaplan, EMBO Mol Med 2010(Aug 18) [Epub ahead of print][Full text]. Abstract:

Neuroblastoma (NB) is the most deadly extra-cranial solid tumour in children necessitating an urgent need for effective and less toxic treatments. One reason for the lack of efficacious treatments may be the inability of existing drugs to target the tumour-initiating or cancer stem cell population responsible for sustaining tumour growth, metastases and relapse. Here, we describe a strategy to identify compounds that selectively target patient-derived cancer stem cell-like tumour-initiating cells (TICs) while sparing normal paediatric stem cells (skin-derived precursors, SKPs) and characterize two therapeutic candidates. DECA-14 and rapamycin were identified as NB TIC-selective agents. Both compounds induced TIC death at nanomolar concentrations in vitro, significantly reduced NB xenograft tumour weight in vivo, and dramatically decreased self-renewal or tumour-initiation capacity in treated tumours. These results demonstrate that differential drug sensitivities between TICs and normal paediatric stem cells can be exploited to identify novel, patient-specific and potentially less toxic therapies.

See also: New Twist on Drug Screening to Treat Common Childhood Cancer, ScienceDaily, August 18, 2010. Excerpt:

A study led by scientists at The Hospital for Sick Children (SickKids) reveals a new method of identifying drugs to treat children suffering from fatal cancers for which an effective treatment has not been found. Rather than developing a new drug from scratch, which is a complicated and time-consuming process, they tried a different approach: in the lab, they tested existing drugs on cancer stem cells from young patients with neuroblastoma, one of the common cancers of infants and children.

A related blog post is: High-throughput cancer stem cell-based screening assay for therapeutic compounds by Alexey Bersenev, Stem Cell Assays, August 19, 2010 [FriendFeed entry].

Two Open Access reviews

1) Cancer Stem Cells in Pancreatic Cancer by Qi Bao and 6 co-authors, including Karl-Walter Jauch and Christiane J Bruns, Cancers 2010(Aug 19); 2(3): 1629-41. [Full text PDF][Scribd entry][Part of the Special Issue Pancreatic Cancer]. Abstract:

Pancreatic cancer is an aggressive malignant solid tumor well-known by early metastasis, local invasion, resistance to standard chemo- and radiotherapy and poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated and propagated by cancer stem cells (CSCs). Here we review the current research results regarding CSCs in pancreatic cancer and discuss the different markers identifying pancreatic CSCs. This review will focus on metastasis, microRNA regulation and anti-CSC therapy in pancreatic cancer.

2) The Emerging Role of the Phosphatidylinositol 3-Kinase/ Akt/Mammalian Target of Rapamycin Signaling Network in Cancer Stem Cell Biology by Alberto M Martelli and 4 co-authors, including James A McCubrey, Cancers 2010(Aug 18); 2(3): 1576-96. [Part of the Special Issue Cancer Stem Cells].

Comment: Review #2 is the first paper that has been published in the special issue on Cancer Stem Cells. As of August 20, 17 more contributions to this special issue are planned. Review #1, although about CSCs, is a contribution to a separate special issue on Pancreatic Cancer.

Therapeutic implications of colon CSCs

Therapeutic implications of colon cancer stem cells by Eros Fabrizi and 3 co-authors, including Lucia Ricci-Vitiani, World J Gastroenterol 2010(Aug 21); 16(31): 3871-7. OA review. [FriendFeed entry][PubMed citation]. Abstract:

Colorectal cancer is the second most common cause of cancer-related death in many industrialized countries and is characterized by a heterogenic pool of cells with distinct differentiation patterns. Recently, the concept that cancer might arise from a rare population of cells with stem cell-like properties has received support with regard to several solid tumors, including colorectal cancer. According to the cancer stem cell hypothesis, cancer can be considered a disease in which mutations either convert normal stem cells into aberrant counterparts or cause a more differentiated cell to revert toward a stem cell-like behaviour; either way these cells are thought to be responsible for tumor generation and propagation. The statement that only a subset of cells drives tumor formation has major implications for the development of new targeted therapeutic strategies aimed at eradicating the tumor stem cell population. This review will focus on the biology of normal and malignant colonic stem cells, which might contribute to our understanding of the mechanisms responsible for tumor development and resistance to therapy.

Putative tumor-initiating progenitor cells predict poor lung cancer prognosis

Adult lung stem cells, vital to injury repair, associated with poor cancer prognosis, News release, UCLA Newsroom, August 17, 2010. Excerpts:

Adult stem cells that are vital for airway repair in the lung but that persist in areas where pre-cancerous lesions are found are associated with a poor prognosis in patients who develop cancer, even those with early-stage disease, researchers at UCLA's Jonsson Comprehensive Cancer Center have found.

.....

In this study, Gomperts and her team screened around 900 tumors removed from patients with non-small cell lung cancer at UCLA and the University of Texas' MD Anderson Cancer Center, looking to see whether the adult stem cells could be found in the tumor. In her lab, Gomperts is now studying the pre-cancerous lesions where the adult stem cells persist in an attempt to uncover the cascade of molecular events that may transform these cells into lung cancer stem cells.

The news release is based on this publication: Presence of a Putative Tumor-Initiating Progenitor Cell Population Predicts Poor Prognosis in Smokers with Non–Small Cell Lung Cancer by Aik T Ooi and 19 co-authors, including Brigitte N Gomperts, Cancer Res 2010(Aug 15); 70(16): 6639-48. [PubMed citation][Full text]. Abstract:

Smoking is the most important known risk factor for the development of lung cancer. Tobacco exposure results in chronic inflammation, tissue injury, and repair. A recent hypothesis argues for a stem/progenitor cell involved in airway epithelial repair that may be a tumor-initiating cell in lung cancer and which may be associated with recurrence and metastasis. We used immunostaining, quantitative real-time PCR, Western blots, and lung cancer tissue microarrays to identify subpopulations of airway epithelial stem/progenitor cells under steady-state conditions, normal repair, aberrant repair with premalignant lesions and lung cancer, and their correlation with injury and prognosis. We identified a population of keratin 14 (K14)-expressing progenitor epithelial cells that was involved in repair after injury. Dysregulated repair resulted in the persistence of K14+ cells in the airway epithelium in potentially premalignant lesions. The presence of K14+ progenitor airway epithelial cells in NSCLC predicted a poor prognosis, and this predictive value was strongest in smokers, in which it also correlated with metastasis. This suggests that reparative K14+ progenitor cells may be tumor-initiating cells in this subgroup of smokers with NSCLC.

ISCO to Present Data on Progress of Human Parthenogenetic Stem Cell Differentiation into Functional Liver Cells at the Annual Meeting…

ISCO to Present Data on Progress of Human Parthenogenetic Stem Cell Differentiation into Functional Liver Cells at the Annual Meeting of the American Association for the Study of Liver Diseases

International Stem Cell Corporation (OTCBB:ISCO), http://www.internationalstemcell.com, will present data on its progress toward producing human liver cells from immune-matched patient-specific parthenogenetic stem cells at The Liver Meeting®, the 61st Annual Meeting of the American Association for the Study of Liver Diseases (ASSLD), in Boston, MA from October 29 – November 2, 2010.

ISCO will present to a number of the world's leading liver specialists, a new method of obtaining highly enriched cultures of differentiated cells from pluripotent human stem cells, based on a natural physiological process. A follow-on presentation will demonstrate that differentiation protocols previously developed for human embryonic stem cells can, with some modification, be effectively applied to human parthenogenetic stem cells. These findings will be presented as part of the 'Stem Cell Poster Session' on November 1, 2010, and are entitled, 'Hepatocyte-like cells derived from patient-specific human parthenogenetic stem cells possess functions of mature human hepatocytes including P450 activity" and, "Derivation of highly enriched populations of hepatocytes from various types of human pluripotent stem cells using a novel physiological method."

Commenting on these presentations, ISCO's CEO, Andrey Semechkin, PhD, said: "We are pleased our research team is able to present and discuss these important findings at this highly prestigious meeting of The American Association for the Study of Liver Diseases, one of the leading organizations in the U.S. specializing in the health of the liver and attended by more than 7,500 physicians and scientists."

ISCO's Director of Research and Therapeutic Development, Nikolay Turovets, PhD, stated, "Presenting these new discoveries at this meeting demonstrates the progress we have made towards producing hepatic cells using our parthenotes, and form part of our ongoing efforts to develop and publicize the unique benefits of our human parthenogenetic stem cell platform to the scientific community. Over the past year, our research group has also presented data to the International Society for Stem Cell Research (ISSCR), the 8th Annual Meeting and the Human SCNT Workshop conducted by the California Institute for Regenerative Medicine (CIRM) and the Medical Research Council (MRC)".

In addition, ISCO announced today the signing of an agreement with Explora BioLabs, a leading California-based CRO specializing in conducting high-quality pre-clinical in vivo studies. Based on the results presented at this conference, ISCO will be initiating a series of pre-clinical animal experiments to study the engraftment and in vivo maturation of these cells.

ISCO's Vice President, Simon Craw, PhD, said: "Demonstrating that our human parthenogenetic stem cells can truly differentiate into mature cells, as well as the initiation of these animal studies represents important achievements towards demonstrating the validity of creating a bank of immune-matched human pluripotent stem cells and their therapeutic derivatives that can be used in clinical studies and, ultimately, be a valuable health resource for the growing field of regenerative medicine."

ABOUT INTERNATIONAL STEM CELL CORPORATION (ISCO.OB)

International Stem Cell Corporation is a California-based biotechnology company focused on therapeutic and research products. ISCO's core technology, parthenogenesis, results in creation of pluripotent human stem cells from unfertilized oocytes (eggs). These proprietary cells avoid ethical issues associated with use or destruction of viable human embryos and, unlike most other major stem cell types, can be immune matched and be a source of therapeutic cells with minimal rejection after transplantation into hundreds of millions of individuals of differing racial groups. ISCO also produces and markets specialized cells and growth media for therapeutic research worldwide through its subsidiary, Lifeline Cell Technology, and is developing a line of cosmeceutical products via its subsidiary, Lifeline Skin Care. ISCO is advancing novel human stem cell-based therapies where cells have been proven to be efficacious but traditional small molecule and protein therapeutics have not. More information is available on ISCO's website, http://www.internationalstemcell.com.

To subscribe to receive ongoing corporate communications please click on the following link: http://www.b2i.us/irpass.asp?BzID=1468&to=ea&s=0.

FORWARD-LOOKING STATEMENTS

Statements pertaining to anticipated developments and therapeutic applications, the potential benefits of collaborations, affiliations, and other opportunities for the company and its subsidiaries, along with other statements about the future expectations, beliefs, goals, plans, or prospects expressed by management constitute forward-looking statements. Any statements that are not historical fact (including, but not limited to statements that contain words such as "will," "believes," "plans," "anticipates," "expects," "estimates,") should also be considered to be forward-looking statements. Forward-looking statements involve risks and uncertainties, including, without limitation, risks inherent in the development and/or commercialization of potential products and the management of collaborations, uncertainty in the results of clinical trials or regulatory approvals, need and ability to obtain future capital, application of capital resources among competing uses, and maintenance of intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements and as such should be evaluated together with the many uncertainties that affect the company's business, particularly those mentioned in the cautionary statements found in the company's Securities and Exchange Commission filings. The company disclaims any intent or obligation to update forward-looking statements.

Key Words: Stem cells, parthenogenesis, biotechnology

International Stem Cell Corporation
Ken Aldrich, Chairman
1-760-940-6383
kaldrich@intlstemcell.com
or
Nikolay Turovets, PhD
nturovets@intlstemcell.com

International Stem Cell Corporation Reports Significant Progress Towards Creation of the First Bank of Immune-Matched Human Parthenogenetic Stem Cells

International Stem Cell Corporation (OTCBB:ISCO), http://www.internationalstemcell.com, announced today that its oocyte collection and activation protocol has received the approval of an Institutional Review Board (IRB). IRB review and approval is a Federal requirement for all studies enrolling human subjects, and ensures appropriate subject safety and monitoring to protect subjects from unnecessary medical risks. 'Obtaining IRB approval for our oocyte collection and activation protocol is a major step forward towards the goal of building a viable bank of human parthenogenetic stem cells,' said Dr. Simon Craw, Vice President of ISCO.

ISCO's breakthrough discoveries have resulted in unique stem cells carrying distinct advantages over other human pluripotent stem cells. ISCO uses unfertilized eggs (oocytes) to create human 'parthenogenetic' stem cells (hpSCs). Like human embryonic stem cells (hESCs), hpSCs are pluripotent, i.e. they have the capacity to become almost any cell type in the body, yet avoid ethical issues associated with use or destruction of viable human embryos. Unlike hESCs, hpSCs can be created in a form such that they can be immunologically matched to millions of individuals. This makes possible, for the first time, the establishment of a bank containing a manageable number of stem cell lines immune matched to a large patient population.

ISCO also announced that Prof. M. Kalichman of the University of California San Diego and Director of the San Diego Research Ethics Consortium has been engaged to provide help in creating an effective system for the ethical review of ISCO's donor recruitment processes including facilitating Stem Cell Research Oversight (SCRO) committee review and approval. SCRO committee review involves the analysis and approval of the scientific rationale, including any ethical considerations associated with stem cell research. The SCRO committee membership is mandated to include an ethicist, an assisted reproductive technology expert, appropriate scientific expertise, a patient advocate and a non-scientific member of the public.

Prof. Kalichman said, 'I look forward to working with International Stem Cell Corporation to help with both identifying and recommending solutions to the challenges of conducting ethically responsible research with human stem cells.'

These achievements mark major milestones along ISCO's strategic path of leveraging its discoveries and intellectual property to create a bank of immune matched pluripotent human stem cells and their therapeutic derivatives that can be used for clinical research and ultimately as a valuable medical resource to the growing field of regenerative medicine.

ABOUT INTERNATIONAL STEM CELL CORPORATION (ISCO.OB)

International Stem Cell Corporation is a California-based biotechnology company focused on therapeutic and research products. ISCO's core technology, parthenogenesis, results in creation of pluripotent human stem cells from unfertilized oocytes (eggs). These proprietary cells avoid ethical issues associated with use or destruction of viable human embryos and, unlike most other major stem cell types, can be immune matched and be a source of therapeutic cells with minimal rejection after transplantation into hundreds of millions of individuals of differing racial groups. ISCO also produces and markets specialized cells and growth media for therapeutic research worldwide through its subsidiary, Lifeline Cell Technology, and is developing a line of cosmeceutical products via its subsidiary, Lifeline Skin Care. ISCO is advancing novel human stem cell-based therapies where cells have been proven to be efficacious but traditional small molecule and protein therapeutics have not. More information is available at ISCO's website, http://www.internationalstemcell.com.

To subscribe to receive ongoing corporate communications please click on the following link: http://www.b2i.us/irpass.asp?BzID=1468&to=ea&s=0.

FORWARD-LOOKING STATEMENTS

Statements pertaining to anticipated technological developments and therapeutic applications, the potential benefits of collaborations, affiliations, and other opportunities for the company and its subsidiaries, along with other statements about the future expectations, beliefs, goals, plans, or prospects expressed by management constitute forward-looking statements. Any statements that are not historical fact (including, but not limited to statements that contain words such as "will," "should," "believes," "plans," "anticipates," "expects," "estimates,") should also be considered to be forward-looking statements. Forward-looking statements involve risks and uncertainties, including, without limitation, risks inherent in the development and/or commercialization of potential products, uncertainty in the results of clinical trials or regulatory approvals, need and ability to obtain future capital, application of capital resources among competing uses, and maintenance of intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements and as such should be evaluated together with the many uncertainties that affect the company's business, particularly those mentioned in the cautionary statements found in the company's Securities and Exchange Commission filings. The company disclaims any intent or obligation to update these forward-looking statements.

Key Words: Stem Cells, Biotechnology, Parthenogenesis

International Stem Cell Corporation
Kenneth C. Aldrich, Chairman
760-940-6383
kaldrich@intlstemcell.com
or
Simon Craw, PhD, Vice President
760-940-6383
sc@intlstemcell.com

A Primer on the Use of Stem Cells in Ophthalmology by Irving J. Arons

An extremely comprehensive article about stem cell programs in opthalmology by Irving J. Arons

A Primer on the Use of Stem Cells in Ophthalmology
by Irving J. Arons

I recently came across an interesting news release from International Stem Cell Corporation (ISCO) announcing that it had formed a new business unit, Cytovis, to focus on stem cell programs in ophthalmology, including CytoCor for the cornea and CytoRet for the retina.

That got me thinking about how little I knew about what was going on in stem cell research in ophthalmology, despite having written about two developments in the field, the London Project to Cure Blindness and the University of California Irvine (UCI) program to develop an artificial retina based on stem cell research.

I decided to become better informed by taking a closer look at what was happening in this field, and presenting that story.

Introduction
Commenting on a EuroRetina Meeting held earlier in 2008, John Morrow of Newport Biotech Consultants noted, as reported by Ophthalmology Times Europe in September 2008, “Stem Cells are looked upon as either an ethical train wreck or the gateway to the alleviation of human illness, depending on which side of the political spectrum one resides. This unfortunate notoriety has resulted in unprecedented coverage in the media, but this has not done much to advance the cause of this technology. Yet recent ophthalmologic research suggests that the medical applications of stem cells hold notable promise for the treatment of ocular degenerative conditions and that realization of this potential may come about in the near future.”

I think Dr. Morrow’s thoughts eloquently sum up the subject. Stem cell research is politically charged but holds tremendous promise for the future, especially in ophthalmology.

What are Stem Cells?
Every organ and tissue in our bodies is made up of specialized cells that originally come from a pool of stem cells in the very early embryo (“embryonic stem cells”). Throughout our lives we rely to a much more limited degree on rare deposits of stem cells in certain areas of the body (“adult stem cells”) to regenerate organs and tissues that are injured or lost, such as our skin, our hair, our blood and the lining of our gut.

Stem cells are like a blank microchip that can be programmed to perform particular tasks. Under proper conditions, stem cells develop or “differentiate” into specialized cells that carry out a specific function, such as in the skin, muscle, liver, or in the eye. Additionally, stem cells can grow extensively without differentiating and give rise to more stem cells...

To read the full article, please visit - http://irvaronsjournal.blogspot.com/2010/09/primer-on-use-of-stem-cells-in.html

Kenneth Aldrich, Chairman and Co-Founder of International Stem Cell Corporation will be making two public appearances this week on behalf of ISCO.

On Monday, September 13, 2010, Mr. Aldrich will be speaking as part of a panel at the Stem Cells USA & Regenerative Medicine Congress in Philadelphia, discussing the topic, "Autologous vs. Allogeneic Business Models".
On Wednesday, September 15, 2010 at 9:35AM EDT, Mr. Aldrich will present at the Rodman and Renshaw Annual Global Investment Conference in New York. The webcast can be viewed live at: http://www.wsw.com/webcast/rrshq18/isco.ob. The presentation will be archived and viewable at the same link for 90 days. After the Rodman and Renshaw Conference, a link to the presentation will also be posted to the ISCO website, http://www.internationalstemcell.com.

International Stem Cell Corporation Not Adversely Affected by Stem Cell Research Funding Ban

OCEANSIDE, CA – August 26, 2010 – International Stem Cell Corporation (OTCBB:ISCO), http://www.internationalstemcell.com, announced today that the recent action of a federal district judge blocking federal funding of embryonic stem cell research is not expected to have negative effects on ISCO’s therapeutic programs using its human parthenogenetic stem cells.

According to ISCO’s Chairman Ken Aldrich, “Because we have never depended on federal or state money to fund our research, the new ruling is simply not applicable to any of our programs in the US or any of our international efforts. Although we believe anything that restricts legitimate scientific research is detrimental to science and our Country and hope the ruling is quickly reversed, the ruling could in a strange way benefit ISCO by creating additional incentives for researchers to use our parthenogenetic stem cell lines.”

Because ISCO’s technology, parthenogenesis, does not destroy or damage a viable human embryo, its parthenogenetic stem cell lines (“hpSC”) offer an alternative way to continue research previously done with embryonic cell lines without raising ethical issues about the destruction of life. Published peer-reviewed papers have shown hpSC to be “pluripotent”, a characteristic shared with embryonic stem cells that allows them to become tissues leading to all the cells found in the human body. Therefore, ISCO’s hpSC lines offer an alternative to the ethical issues that continue to be problematic for embryonic stem cells.

When enacted, legislation prohibiting the creation of a human embryo for research purposes prohibited both successful methods, such as fertilization, as well as less understood methods such as parthenogenesis. Parthenogenetic methods since developed by ISCO do not create human embryos that could become viable human beings, yet can result in pluripotent hpSC lines with potential therapeutic value. “The recent court ruling may cause Congress to revisit its legislation. If so, then ISCO’s research showing its hpSC lines present an alternative to embryonic stem cells, without raising the ethical concerns about the creation or destruction of viable human life, may lead to Congress allowing federal funding of hpSC in future legislation. ISCO would then be free to provide hpSC lines to federally-funded researchers and move more of our work back into the US from foreign jurisdictions”, said Jeffrey Janus, Senior Vice President of ISCO and one of its founders.

ABOUT INTERNATIONAL STEM CELL CORPORATION (ISCO.OB)
International Stem Cell Corporation is a California-based biotechnology company focused on therapeutic and research products. ISCO's core technology, parthenogenesis, results in creation of pluripotent human stem cells from unfertilized oocytes (eggs). These proprietary cells avoid ethical issues associated with use or destruction of viable human embryos and, unlike all other major stem cell types, can be immune matched and be a source of therapeutic cells with minimal rejection after transplantation into hundreds of millions of individuals across racial groups. ISCO also produces and markets specialized cells and growth media for therapeutic research worldwide through its subsidiary Lifeline Cell Technology, develops a line of cosmeceutical products via its subsidiary Lifeline Skin Care and advances novel human stem cell-based therapies where cells have been proven to be efficacious but traditional small molecule and protein therapeutics do not. More information is available at ISCO's website, http://www.internationalstemcell.com.

To subscribe to receive ongoing corporate communications please click on the following link: http://www.b2i.us/irpass.asp?BzID=1468&to=ea&s=0

FORWARD-LOOKING STATEMENTS
Statements pertaining to anticipated technological developments and therapeutic applications, the potential benefits of collaborations, affiliations, and other opportunities for the company and its subsidiaries, along with other statements about the future expectations, beliefs, goals, plans, or prospects expressed by management constitute forward-looking statements. Any statements that are not historical fact (including, but not limited to statements that contain words such as "will," "should," "believes," "plans," "anticipates," "expects," "estimates,") should also be considered to be forward-looking statements. Forward-looking statements involve risks and uncertainties, including, without limitation, risks inherent in the development and/or commercialization of potential products, uncertainty in the results of clinical trials or regulatory approvals, need and ability to obtain future capital, application of capital resources among competing uses, and maintenance of intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements and as such should be evaluated together with the many uncertainties that affect the company's business, particularly those mentioned in the cautionary statements found in the company's Securities and Exchange Commission filings. The company disclaims any intent or obligation to update these forward-looking statements.

Key Words: Stem Cells, Biotechnology, Parthenogenesis

CONTACTS:
International Stem Cell Corporation
Kenneth C. Aldrich, Chairman
760-940-6383
kaldrich@intlstemcell.com
Or
Jeffrey Janus
Sr. Vice President, Operations
760-640-6383
jjanus@intlstemcell.com

International Stem cell Corporation Chairman Discusses Recent Stem Cell Research Funding Decision

This is Ken Aldrich and I am Chairman of International Stem Cell Corporation and I thought I should comment briefly on the recent decision of the federal district court of the District of Columbia concerning stem cell research.

What the court did was to announce that it was prohibiting the use of federal funding by the NIH for embryonic stem cell research which is a major blow if the decision is upheld for the stem cell industry. It’s interesting because it actually does not affect International Stem Cell Corporation in any direct negative manner.

The truth of the matter is we have not been able to use federal funding since the very beginning of the company because of a particular provision in the Dickey Wicker amendment that specifically calls out parthenogenic stem cells as a form of embryo, in spite of the fact that they genuinely are not an embryo in fact cannot ever become any living human being and don’t involve the destruction of anything that could become human being. Nevertheless, we have always been caught up in the Dickey Wicker amendment. So we haven’t been hurt by this decision, if anything it has perhaps leveled the playing field for us a bit with the embryonic stem cell group.

But the bottom line is we don’t really think it is good for the country and we hope there will be a change. But we do hope is that perhaps this will open the political debate and as people begin to look at the broader spectrum and realize that parthenogenic stem cell, which is our stock and trade, do not involve the destruction of any embryos, it may be that the specific language of the Dickey Wicker amendment can ultimately be removed and we would then become eligible along with everyone else for federal funding through the NIH and other government programs. If so, it would be a wonderful result. In the meantime, it is a difficult time for everyone in the industry. We’ll keep you informed. Thank you

Revisiting the Free Radical Theory of Aging

Thoughts on the impact of better technology on free radical theory: "The role of oxidative stress in aging proposed by the free radical theory has been the focus of investigations for more than fifty years. The results of a large number of these investigations provide support for this theory. However, numerous recent findings point to the existence of unexpected complexity in the relationships between oxidative stress and aging. This complexity is highlighted by the discovery [that] a key element of oxidative stress defenses in the model organism budding yeast, shortens lifespan in concert with enhanced resistance to oxidative stress. In addition to the implications of this finding for understanding aging, identification of this mutation by massively parallel sequencing of whole genomes emphasizes the enormous utility of next-generation sequencing technologies as investigative tools that will likely revolutionize genetics. ... In some cases, the apparent disconnect between experimental results and predictions of the free radical theory regarding connections between oxidative stress and lifespan is related to hormesis effects that elevate oxidative and other stress defenses in response to low levels of oxidative stress. ... The more transparently clear lesson here is that not all forms of oxidative stress are equivalent in their effects on aging. This isn't surprising in the context of the multitude of pathways that respond to different forms of oxidative stress and the numerous mechanisms by which oxidants can modify different macromolecular targets. Whatever the explanation, [research findings] emphasize the enormous complexity of relationships between oxidative stress and aging."

View the Article Under Discussion: http://www.impactaging.com/papers/v2/n8/full/100188.html

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

Early Development, Moose, and Later Arthritis

From the New York Times: "In the 100 years since the first moose swam into Lake Superior and set up shop on an island, they have mostly minded their moosely business, munching balsam fir and trying to evade hungry gray wolves. But now the moose of Isle Royale have something to say - well, their bones do. Many of the moose, it turns out, have arthritis. And scientists believe their condition's origin can help explain human osteoarthritis - by far the most common type of arthritis, affecting one of every seven adults 25 and older and becoming increasingly prevalent. The arthritic Bullwinkles got that way because of poor nutrition early in life, an extraordinary 50-year research project has discovered. That could mean, scientists say, that some people's arthritis can be linked in part to nutritional deficits, in the womb and possibly throughout childhood. The moose conclusion bolsters a small but growing body of research connecting early development to chronic conditions like osteoarthritis. ... Nutrients, experts say, might influence composition or shape of bones, joints or cartilage. Nutrition might also affect hormones, the likelihood of later inflammation or oxidative stress, even how a genetic predisposition for arthritis is expressed or suppressed."

View the Article Under Discussion: http://www.nytimes.com/2010/08/17/health/research/17moose.html

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

Video: Summary of Recent Developments in Stem Cell and Regenerative Medicine from Kenneth Aldrich, Chairman of International Stem Cell Corporation

Greetings. This is Ken Aldrich, I am Chairman of International Stem Cell Corporation and thought I would share with you briefly some of the thoughts that I’ve had recently about developments in the stem cell and regenerative medicine area. One of the things that I have noticed from a lot of emails that we get, there is a fair amount of confusion out there about the significance of some of the new events that have taken place.

Specifically, I have gotten a lot of requests to explain what the impact of the recent announcement by Geron Corporation that they had entered FDA human trials might be. Well frankly, it is a very, very important step and one that benefits, I think, everyone in our industry and I wanted to comment on it a little bit. What that means is that one of the companies in our field has finally found the mechanism and found the procedures to begin the process of bringing cells to the clinic through human trials. So Geron, which is one of the largest companies, and has spent an enormous amount of money developing this, is now leading the path for all of us. I think we will learn from their experiences and it will make the path getting through to the FDA a lot more productive for all of us that follow.

There is another aspect to this however, that is unique to our company, International Stem Cell Corporation, in that we have also realized that the United States in only one part of the global market. And as a result, we’ve spent a lot of energy over the last year or so exploring foreign collaborations in those areas where perhaps the US is not the most attractive market. For example, we are working in India with replacing human corneas with corneas developed from our parthenogenic stem cells. The U.S. is probably not a major market for this because our systems here in this country allow for cornea transplants rather well. But in countries like India, as well as China and Korea and other places, the infrastructure doesn’t exist to harvest corneas from cadavers and deliver them and as a result, we have a wide open market there with enormous interest. I think that is one example of how the international market will impact the development of regenerative medicine.

We’re looking at that and we are looking at a variety of other areas and I’m sure other companies are doing the same. Eventually, we are all in this boat together to try to cure major diseases. We’re delighted with the progress with the FDA from companies here. We’ll be following in those footsteps when we can and we also be hopefully be leading the way in some of the international collaborations that may make all of us better off in the world of regenerative medicine.

Thank you.

Investigating the Aging of Stem Cells

From the Korea Times: "Stem cells, or early-stage cells that retain the potential to turn into other specialized types of cells, are intriguing for their immense potential in treating a wide range of difficult diseases and conditions. And holding an important key to such innovations would be adult stem cells, which are taken from mature tissue, as they could theoretically be taken from patients, grown in culture and transplanted back into the patient without the fear of provoking an immune response. ... The downside of adult stem cells, however, is that they age much faster than embryonic cells, which has limited their usefulness in transplants. ... It has been presumed that the decreasing regenerative capacity of adult stem cells, which is linked to their aging, is a result of inborn genetic variations. But [researchers suggest] that the process isn't dictated by heritable events, such as DNA damage, but rather determined by an 'epigenetic' regulation of gene expression. ... There weren't many studies on finding micro-RNAs related to the aging of cells and learn how they affect stem cells, but this area could be important in developing a way to have adult stem cells retain their normal ability for a longer time."

View the Article Under Discussion: http://www.koreatimes.co.kr/www/news/tech/2010/08/133_71494.html

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What We Know About Fat Tissue and Longevity

In a nutshell: "Adipose tissue accounts for approximately 20% (lean) to [more than] 50% (in extreme obesity) of body mass and is biologically active through its secretion of numerous peptides and release and storage of nutrients such as free fatty acids. Studies in rodents and humans have revealed that body fat distribution, including visceral fat (VF), subcutaneous (SC) fat and ectopic fat are critical for determining the risk posed by obesity. Specific depletion or expansion of the VF depot using genetic or surgical strategies in animal models has proven to have direct effects on metabolic characteristics and disease risk. In humans, there is compelling evidence that abdominal obesity most strongly predicts mortality risk, while in rats, surgical removal of VF improves mean and maximum life span. There is also growing evidence that fat deposition in ectopic depots such as skeletal muscle and liver can cause lipotoxicity and impair insulin action. Conversely, expansion of SC adipose tissue may confer protection from metabolic derangements by serving as a 'metabolic sink' to limit both systemic lipids and the accrual of visceral and ectopic fat. Treatments targeting the prevention of fat accrual in these harmful depots should be considered as a primary target for improving human health span and longevity."

View the Article Under Discussion: http://www.ncbi.nlm.nih.gov/pubmed/20703052

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