StemCell Therapy

Northern Exposure by Emmet Pierce, San Diego Business Journal, August 16, 2010. Excerpt:

An example of San Diegans collaborating with Canadians is the work that has taken place at the UC San Diego Moores Cancer Center in cooperation with research at the University of Toronto. The partnership has enabled San Diego researchers to acquire a $20 million grant to develop drugs to be used against leukemia stem cells, Barr says.Dr. Catriona Jamieson, director of the stem cell research program at the Moores center, said scientists from Toronto and San Diego share "a deep and abiding interest in cancer stem cell biology." The Canadian consulate in San Diego was instrumental in helping to create a relationship in which both institutions would benefit, sharing information and applying for funds to support their research.

"The idea was to establish a Canada-California cancer stem cell initiative and obtain connections with Canadian funding agencies, particularly Genome Canada and the Ministry of Health," she said.

Jamieson added, "The most important thing is it allows people with disparate abilities and backgrounds to work together on the same problem."

Barr said the University of Toronto also was able to secure a $20 million research grant because of the collaboration, "so the team is greater than the sum of its parts."

Oxygen in Stem Cell Biology: A Critical Component of the Stem Cell Niche by Ahmed Mohyeldin, Tomás Garzón-Muvdi and Alfredo Quiñones-Hinojosa, Cell Stem Cell 2010(Aug 6); 7(2): 150-61. Review. [PubMed citation][FriendFeed entry]. Via Twitter @CellStemCell: Access [to the full text] is free in August worldwide so readers can try out new enhanced online format.

Abstract:

The defining hallmark of stem cells is their ability to self-renew and maintain multipotency. This capacity depends on the balance of complex signals in their microenvironment. Low oxygen tensions (hypoxia) maintain undifferentiated states of embryonic, hematopoietic, mesenchymal, and neural stem cell phenotypes and also influence proliferation and cell-fate commitment. Recent evidence has identified a broader spectrum of stem cells influenced by hypoxia that includes cancer stem cells and induced pluripotent stem cells. These findings have important implications on our understanding of development, disease, and tissue-engineering practices and furthermore elucidate an added dimension of stem cell control within the niche.

The following is an excerpt from the August 3, 2010 Breakthrough Technology Alert, published by Agora Financial. Agora Financial is a fully independent publisher and has no financial connections to companies listed below. Breakthrough Technology Alert's editor is industry expert Patrick Cox. Patrick is renowned for his innovative forecasts and keeping readers "ahead of the story".

For more information about Patrick Cox and Breakthrough Technology Alert please visit http://www.agorafinancial.com

ISCO Collaborations Accelerate

Last week, I told you about International Stem Cell Corp.'s (OTCBB: ISCO) new European subsidiary, ISCO Europe. That announcement closely followed an announced alliance with a leading Indian provider of corneal transplants. Now ISCO has announced that it has entered into a distribution agreement for its Lifeline brand of human cell culture products in India.

Jeffrey Janus, senior vice president of operations of ISCO and CEO of its subsidiary Lifeline, said in a press release, Sristi Biosciences is part of one of the most experienced biotechnology companies in India and the first to advance cell therapy into human trials in that country. Their network among academic and corporate researchers and experience and capacity to import and handle primary cell cultures, media and growth factors in India will be highly valuable for Lifeline to continue the international commercial expansion of its brand.

For transformational profits,

Patrick Cox

To learn more about Patrick Cox and Breakthrough Technology Alert please click here. © 2010 by Agora Financial, LLC. 808 St. Paul Street, Baltimore, MD 21202. All rights reserved. No part of this report may be reproduced by any means or for any reason without the consent of the publisher. The information contained herein is obtained from sources believed to be reliable; however, its accuracy cannot be guaranteed.

Scientists at UCLA find cell of origin for human prostate cancer by Kim Irwin, UCLA Newsroom, July 29, 2010. Excerpts:

"Certainly, the dominant thought is that human prostate cancer arose from the luminal cells because the cancers had more features resembling luminal cells," said Witte, senior author of the study and a Howard Hughes Medical Institute Investigator. "But we were able to start with a basal cell and induce human prostate cancer, and now, as we go forward, this gives us a place to look in understanding the sequence of genetic events that initiates prostate cancer and defining the cell-signaling pathways that may be at work fueling the malignancy, helping us to potentially uncover new targets for therapy."

.....

The new human-in-mouse model system developed in the study was created by taking healthy human prostate tissue that will induce cancer once it is placed in mice, instead of taking malignant tissue that is already cancerous and implanting it. This model can now be used to evaluate the effectiveness of new types of therapeutics. By using defined genetic events to activate specific signaling pathways, researchers can more easily compare therapeutic efficacy. The new model, by deconstructing tissue and then reconstructing it, also will aid in analyzing how the cells change during cancer progression.

This news release is based on the publication: Identification of a Cell of Origin for Human Prostate Cancer by Andrew S Goldstein and 5 co-authors, including Owen N Witte, Science 2010(Jul 30); 329(5991): 568-71. [PubMed citation][FriendFeed entry][Twitter trackbacks via Topsy].

The Evolving Science of Cancer Stem Cells by Carmen Phillips, NCI Cancer Bulletin 2010(Jul 27); 7(15). Excerpt:

Researchers from Stanford University earlier this month reported in Nature that they had found a marker, CD271, that identified a somewhat unique population of cells that could produce melanoma in highly immunocompromised mice; anywhere from 2.5 percent to 41 percent of cells in their human tumor samples expressed the marker. In additional experiments using similar mice on which human skin was engrafted, only tumor cells with the marker could produce tumors and metastases in the mice. (In his lab, Dr. Morrison noted, the same marker did not differentiate tumor-forming from nontumor-forming cells.)

The publication about CD271 is: Human melanoma-initiating cells express neural crest nerve growth factor receptor CD271 by Alexander D Boiko and 11 colleagues, Nature 2010(Jul 1); 466(7302): 133-7. [PubMed citation].

Comments: The sentence: "In his lab, Dr. Morrison noted, the same marker did not differentiate tumor-forming from nontumor-forming cells" is noteworthy. Why the difference in results for CD271?

The publication by Boiko and co-authors was cited in a previous post to this blog, "Melanoma-initiating cells identified", dated July 1, 2010.

See also an earlier post to this blog, "Tumorigenic cells not rare in human melanoma", dated December 3, 2008.

International Stem Cell Corporation (OTCBB:ISCO), http://www.internationalstemcell.com, via its wholly-owned subsidiary, Lifeline Cell Technology® (Lifeline) http://www.lifelinecelltech.com, and Sristi Biosciences, http://www.sristibio.com, have entered into a distribution agreement for the Lifeline® brand of human cell culture products in India.

Lifeline specializes in development, manufacture and distribution of primary human cells and media and growth factors for optimized culturing of cells, including stem cells. These products are being requested by customers internationally, including in India, which represents one of the fastest growing markets for products of this kind.

According to Lifeline's CEO and SVP of Operations at ISCO, Jeffrey Janus, 'Sristi Biosciences is part of one of the most experienced biotechnology companies in India and the first to advance cell therapy into human trials in that country. Their network among academic and corporate researchers and experience and capacity to import and handle primary cell cultures, media and growth factors in India will be highly valuable for Lifeline to continue the international commercial expansion of its brand.'

Lifeline's scientists have over 20 years of experience developing products for the culture of human cells. The company has made significant contributions to the creation and standardization of human cell systems used today for clinical applications and in academic, government and pharmaceutical research laboratories. The group sells over 75 standardized products directly and via its distributors in the US and abroad. It also engages in customized product development for its largest customers.

Dr. Sudhir Reddy, Sristi Biosciences' CEO adds, 'We are pleased to be the first company to introduce the Lifeline products to the growing Indian research market. Our cell culture experience and broad market reach in India will benefit the brand and help Sristi Biosciences further accelerate its commercialization and corporate growth in the biomedical field.'

ISCO recently announced the beginning of a collaboration on its human corneal tissue, CytoCor™, with leading Indian eye hospital and research center, Sankara Nethralaya, and Letter of Intent with Insight Bioventures India (IBVI) to seek funding and establishment of development and manufacturing operations for ISCO's research and pharmaceutical products in India (ISCO India), including the Lifeline products and CytoCor.

'The Lifeline distribution agreement with Sristi Biosciences is central to ISCO's international expansion. Besides facilitating commercialization of the Lifeline products in India, Sristi Biosciences' cell therapy development, regulatory and manufacturing expertise will be important as ISCO and IBVI seek to establish ISCO India with cost-efficient development and manufacturing of research and pharmaceutical products for the Indian and broader Asian markets,' says Brian Lundstrom, ISCO's President.

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.

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.

ABOUT SRISTI BIOSCIENCES

Sristi Biosciences Private Limited is a result of twelve years of research and corporate development in the therapeutic space and is the healthcare component of leading biotechnology group, SRI Biotech, in India. Sristi Biosciences' two main divisions include Tissue Engineering and Cell Therapy that has pioneered chondrocytes-based cell therapy in India and Drug Discoverythat covers the Indian research product market with natural compound libraries, molecular diagnostics and markers, informatics and cell-based products. Sristi's integrated research and development facility in Hyderabad is state-of-the-art and the company has wide collaborative and commercial presence across the research market in India, including 23 leading biotech institutes and major corporate bodies.

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, Biotechnology, Parthenogenesis

International Stem Cell Corporation
Kenneth C. Aldrich, Chairman
760-940-6383
kaldrich@intlstemcell.com
Or
Brian Lundstrom, President
760-640-6383
bl@intlstemcell.com

Researchers Study Cancer Stem Cells as Therapeutic Targets for Mesothelioma, Asbestos.com, July 26, 2010. Excerpt:

In a study published in the International Journal of Oncology, Cortes-Dericks and colleagues tested whether cancer stem cells in malignant pleural mesothelioma express resistance to cisplatin and pemetrexed, two chemotherapy drugs commonly used to treat mesothelioma cancer.

This news item is based on the OA publication entitled: Putative cancer stem cells in malignant pleural mesothelioma show resistance to cisplatin and pemetrexed by Lourdes Cortes-Dericks, Giovanni L Carboni, Ralph A Schmid and Golnaz Karoubi, Int J Oncol 2010(Aug); 37(2): 437-44. [PubMed citation].

Gamma-Tocotrienol Kills Prostate Cancer Stem Cells, PRNewswire, July 25, 2010. Excerpt:

The scientists found that low doses of gamma-tocotrienol cause apoptosis in the prostate cancer stem cells and suppress their colony formation capability. This results in a lower prostate cancer stem cell population (as defined by the protein markers CD133 and CD44). Further tests in mice models were conducted, where mice implanted with hormonal refractory prostate cancer cells were given gamma-tocotrienol orally. The results showed that gamma- tocotrienol not only reduced tumour size formed, but also decreased the incidence rate of tumour formation by 75%, as compared to the control group of mice, which had 100% tumour formation. These results strongly suggest that gamma-tocotrienol could be developed for prostate cancer prevention and treatment.

The news release by Davos Life Science is based on the publication:

Gamma-tocotrienol as an effective agent in targeting prostate cancer stem cell-like population by Sze Ue Luk and 11 co-authors, including Ming-Tat Ling, Int J Cancer 2010(Jul 8) [Epub ahead of print][PubMed citation].

Comment:

See also a relevant patent application: (WO/2010/047663) Use of Tocotrienol Composition for the Prevention of Cancer.
Publication Date: 29.04.2010
Applicants: DAVOS LIFE SCIENCE PTE. LTD. [SG/SG]; 16 Tuas South Street 5 Singapore 637795 (SG) (All Except US).
LING, Ming Tat [CN/AU]; (AU) (US Only).
YAP, Wei Ney [MY/SG]; (SG) (US Only).
WONG, Yong Chuan [MY/CN]; (CN) (US Only).
YAP, Yee Leng, Daniel [MY/SG]; (SG) (US Only).

Irradiating brain's stem cell niche doubles survival time for patients with brain cancers by Kim Irwin, News Release, UCLA Newsroom, July 23, 2010. Excerpt:

Patients with deadly glioblastomas who received high doses of radiation that hit a portion of the brain which harbors neural stem cells had double the progression-free survival time as patients who had lower doses or no radiation targeting the area, a study from the radiation oncology department at UCLA's Jonsson Comprehensive Cancer Center has found.

The news release is based on this OA publication: Irradiation of the Potential Cancer Stem Cell Niches in the Adult Brain Improves Progression-free Survival of Patients with Malignant Glioma by Patrick Evers and 6 co-authors, including Frank Pajonk, BMC Cancer 2010(Jul 21); 10(1):384. [Epub ahead of print][FriendFeed entry].

Comment: On the brain as a model system to study the impact of radiation dose given to stem cell niches. Provides clinical evidence, based on an improvement in progression-free survival, to support the hypothesis that higher radiation doses to neural stem cell (NSC) niches improves patient survival by eradicating CSCs.

International Stem Cell Corporation (OTCBB:ISCO), http://www.intlstemcell.com, announced today that it had entered into a Memorandum of Understanding with ARG Vermogensverwaltung AG ('ARG'), a German Investment Fund, to create a new European subsidiary ('ISCO Europe') to be funded with up to $10 million of capital derived from ARG and other independent sources in Europe. Shares of ISCO Europe are expected to trade on the Deutsche Bourse independently of the company's shares in the US. ISCO Europe's shares will not be convertible into ISCO shares on any US exchange.

ISCO Europe will be licensed by ISCO to develop and market therapeutic products derived from ISCO's technology throughout the Euro Currency Countries and Switzerland. New technologies developed by either ISCO or ISCO Europe will be made mutually available, thus expanding the total funding available to ISCO worldwide without issuing new ISCO shares and enhancing the potential market and scientific development capacity of both companies.

It is expected that the new subsidiary will be funded initially by a private equity investment by ARG and that ARG will then assist in forming an investment group to invest up to $10 million concurrently with the listing of ISCO Europe on the Deutsche Bourse, the largest Securities Exchange in Europe. Following the financing of ISCO Europe, ISCO is expected to retain ownership of 80% or more of this new subsidiary.

'Although negotiations are still at the non-binding memorandum of understanding stage, this transaction, when completed, will expand ISCO's access to capital for worldwide expansion and ISCO's access to new scientific development without requiring equity dilution of ISCO's current shareholders. We are creating an investment, research and development, marketing and distribution entity by adding capital and human resources from Europe to help fulfill ISCO's goal of supplying its proprietary cells and cell therapies to the world,' said Kenneth Aldrich, Chairman and co-founder of ISCO.

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. 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, Biotechnology, Parthenogenesis

International Stem Cell Corporation
Kenneth C. Aldrich, Chairman
760-940-6383
kaldrich@intlstemcell.com
Or
Andrey Semechkin, Ph.D., CEO
aes@intlstemcell.com

New mission for salinomycin in cancer by Cord Naujokat, SciTopics, July 15, 2010. Excerpt (in the "continue reading" section):

In addition, a very recent study demonstrates that salinomycin overcomes ATP-binding cassette (ABC) transporter-mediated multidrug and apoptosis resistance in human leukemia stem cell-like cells (3).

Reference #3: Salinomycin overcomes ABC transporter-mediated multidrug and apoptosis resistance in human leukemia stem cell-like KG-1a cells, by Dominik Fuchs and 4 co-authors, including Cord Naujokat, Biochem Biophys Res Commun 2010(Apr 16);394(4): 1098-104 [Epub 2010(Mar 27)][PubMed citation].

Comments: Near the end of this article about salinomycin is the comment that "the investigation of its safety, toxicity, pharmacology and anticancer activity in humans will be a challenge." The author then mentions a preliminary study of "a small cohort of patients with metastatic breast cancer or metastatic head and neck cancers". The results of this preliminary study of the toxicity of salinomycin are summarized. They have not yet been published in the peer-reviewed literature, although a manuscript has been submitted [see reference #4 in the article]. The implication of these preliminary results is that there may be a "therapeutic window" for salinomycin, that is, a drug dosage that yields clinically significant benefits in the absence of excessive toxicity.

For a previous commentary on salinomycin, see: Cancer stem cell breakthrough by Kat Arney, Science Update blog, Cancer Research UK, August 14, 2009. Excerpt:

We need to stress that these were laboratory experiments, and there is no evidence yet that salinomycin can treat cancer in humans. Salinomycin is currently used as an antibiotic for chickens and cows, and it can be toxic or even fatal to humans, causing serious muscle and heart problems.

If there is a "therapeutic window" for salinomycin, it could be a small one, and is likely to vary from one tumor to another.

For a previous post to this blog about salinomycin, see: Identification of selective inhibitors of breast CSCs in mice, August 14, 2009.

SU2C Innovative Researcher Vlog: Dr. Lawlor (Pt. 3). Video (3:09 min) posted July 13, 2010. Features Elizabeth R Lawlor, University of Michigan, an SU2C Innovative Research Grants Investigator. [About SU2C (Stand Up to Cancer)]. She provides brief comments about her project: "Modeling Ewing Tumor Initiation in Human Neural Crest Stem Cells". How do normal stem cells become cancer stem cells?

An example of a recent (OA) publication from her laboratory: CD133 expression in chemo-resistant Ewing sarcoma cells by
Xiaohua Jiang and 8 co-authors, including Elizabeth R Lawlor,
BMC Cancer 2010(Mar 26); 10: 116. [FriendFeed entry][PubMed citation][Full text via PMC].

Two articles, with Open Access (OA) to the full text (PDF):

Putative cancer stem cells in malignant pleural mesothelioma show resistance to cisplatin and pemetrexed, Int J Oncol 2010(Aug); 37(2): 437-44. [PubMed citation].

Possible involvement of stem-like populations with elevated ALDH1 in sarcomas for chemotherapeutic drug resistance, Oncol Rep 2010(Aug); 24(2): 501-5. [PubMed citation].

Comment about these journals:

Spandidos Publications publishes six journals. Of these six, two are: International Journal of Oncology (2009 Impact Factor: 2.4) and Oncology Reports (2009 Impact Factor: 1.6). This publisher provides a hybrid open access option. The Information for Authors for all six journals includes, at the bottom of the page, this information: "Should authors prefer or require their article to be freely available as soon as it has been published, they may request open access immediately upon publication for a fee of EUR 450."

International Stem Cell Corporation (OTCBB:ISCO), http://www.internationalstemcell.com, and Sankara Nethralaya, http://www.sankaranethralaya.org, announced today commencement of a collaboration to develop ISCO's 'CytoCor™' stem cell-derived corneal tissue. The goal is to use CytoCor to treat corneal blindness and vision impairment. 'This is one more step in ISCO's stated plan of building its portfolio of therapeutic agents through strategic alliances throughout the world,' said Chairman, Ken Aldrich.

CytoCor consists of transparent human tissue derived from pluripotent human stem cells. These structures are produced in the laboratory and recent testing at Sankara Nethralaya and laboratories in the US has demonstrated a range of structural, biochemical and refractory properties characteristic of human cornea.

CytoCor may offer a first-in-class opportunity for high-quality, cost-efficient transplantation tissue for the 10 million people world-wide suffering from corneal vision impairment, particularly in India and the rest of Asia, as well as in Europe. Standardized tissues derived from pluripotent stem cells, such as the CytoCor tissue, could eliminate the current problem that corneal tissue derived from donors may harbor diseases that could be transferred from the donor to the recipient. It may also provide a much needed alternative to the use of live and extracted animal eyes in the $500+million market for safety testing of drugs, chemicals and consumer products.

According to Professor Dr. S. Krishnakumar, 'Sankara Nethralaya is dedicated to the development and application of new state-of-the-art ophthalmic technologies. The need for high-volume, high-quality human corneal tissue is substantial, not only in India but across Asia and much of Europe. We appreciate the opportunity to join ISCO in their pursuit to create a new standard of care for the treatment of human corneal disease.' Initially, Dr. Krishnakumar and his team will be using the CytoCor tissue in preclinical studies to explore the ability of the tissue to withstand sutures and bio-compatible glues in order to validate the potential of the tissue for use in animal or human clinical trials.

According to Dr. Geetha Krishnan Iyer, who is involved in the management of ocular surface disease at Sankara Nethralaya, 'The team at Sankara Nethralaya is pleased to collaborate with ISCO on stem cell-derived corneal tissue. In vitro studies to evaluate safety and efficacy of the tissue, as well as surgical feasibility tests will be carried out, following which there could be clinical application in lamellar keratoplasty using the above mentioned tissue. With improvements in surgical techniques over the past few years, the indications for anterior lamellar keratoplasty have expanded significantly. With high demand for donor corneal tissue for the same but limited availability, there is definitely scope for utilizing ISCO's corneal tissue following relevant tests.'

Jeffrey Janus, Senior VP of Operations at ISCO, states: 'This collaboration with the excellent team of scientists and clinicians at Sankara Nethralaya has already proven to be productive. Sankara's ophthalmology expertise and ISCO's cell culture capabilities constitute a perfect match to perfect and advance CytoCor tissue towards future use in treating corneal disease and injuries.'

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 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, 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 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
Brian Lundstrom, President
760-640-6383
bl@intlstemcell.com

Melanoma-initiating cells identified by study by Krista Conger, News release, Stanford School of Medicine, June 30, 2010. Excerpt:

Scientists at the School of Medicine have identified a cancer-initiating cell in human melanomas. The finding is significant because the existence of such a cell in the aggressive skin cancer has been a source of debate. It may also explain why current immunotherapies are largely unsuccessful in preventing disease recurrence in human patients.

The news release is about this publication: Human melanoma-initiating cells express neural crest nerve growth factor receptor CD271 by Alexander D Boiko and 11 co-authors, including Irving L. Weissman, Nature 2010(Jul 1); 466(7302): 133-7. [FriendFeed entry].

A blog post about this same publication is: Stanford scientists identify a melanoma-initiating cell by Krista Conger, Scope blog, Stanford School of Medicine, June 20, 2010.

See also a commentary about the publication: Cancer stem cells: Invitation to a second round by Peter Dirks, Nature 2010(Jul 1); 466(7302): 40-1. Excerpt:

Boiko et al. study a type of human skin cancer called melanoma and, in particular, cancer cells enriched in a stem-cell marker called CD271. They find that, unlike other cells from the same tumour, CD271-expressing (CD271+) cells could initiate and maintain tumour growth in vivo — an observation consistent with the existence of a melanoma-cell functional hierarchy.

This finding reflects a view different from that of an earlier study by Quintana et al.[3], which demonstrated that, in some cases, as many as 50% of human melanoma cells have tumorigenic potential. In addition, no marker tested identified a tumorigenic subpopulation. The authors[3] concluded that the frequency of cancer cells that can initiate tumorigenesis depends, in part, on the assessment techniques and assays.

Another news item, based on the same publication, is: New hope in fight against skin cancer as deadly 'master cells' are identified for first time, Mail Online, July 1, 2010. Excerpt:

However Dr Alexander Boiko, who made the discovery at Stanford University, said the newly discovered 'stem cells' in advanced skin cancers were often missed by conventional immunotherapy.

'Without wiping out the cells at the root of the cancer, the treatment will fail,' he said.

Comments: Boiko et al. and Dirks suggest reasons why results different from those of Quintana et al. were obtained. One possibility is that the melanomas that the latter authors studied were at an advanced stage. If, as a cancer progresses, more cells acquire the attributes of cancer stem cells, then advanced melanomas may contain very high frequencies of tumorigenic cells.

As Boiko et al. point out in their publication, "The most crucial test of the tumour stem cell hypothesis is that markers or pathways restricted to tumour stem cells can be targets for curative therapies in the patient, which has not yet been done."

The following is an excerpt from the June 29, 2010 Breakthrough Technology Alert, published by Agora Financial. Agora Financial is a fully independent publisher and has no financial connections to companies listed below. Breakthrough Technology Alert’s editor is industry expert Patrick Cox. Patrick is renowned for his innovative forecasts and keeping readers “ahead of the story”.



For more information about Patrick Cox and Breakthrough Technology Alert please visit http://www.agorafinancial.com

Q&A with ISCO



International Stem Cell Corp. (OTCBB: ISCO) has also been the target of rumor campaigns. ISCO, incidentally, recently announced further positive IP news. Specifically, Advanced Cell Technology, Inc. (ACT) was just issued U.S. Patent Number 7736896 covering a method for producing retinal pigment epithelial cells. ISCO, however, had previously acquired rights to this technology from ACT, so the award solidifies their position in stem cell eye therapies.

ISCO's corneal research also got an unexpected boost last week, though it's not clear how many people know it yet. A stem cell breakthrough from Italy made quite a few headlines. The article that provoked the coverage was in the June 23 online version of The New England Journal of Medicine (NEJM). Specifically, it featured clinical research from professor Graziella Pellegrini et al. titled "Limbal Stem-Cell Therapy and Long-Term Corneal Regeneration." A helpful video by ABC News can be viewed here.



The coverage of the journal article is, however, incomplete. So let me put it in perspective.

The procedure made use of the well-established practice of extracting and cultivating limbal stem cells. Each of the patients, in effect, had stem cells removed from at least one eye. Once the adult stem cells were multiplied in the lab, they were applied to the cornea. There, they regenerated the corneal epithelium (the outermost thin layer of the cornea), restoring sight.

This is wonderful proof of the power of stem cells, but it doesn't represent a breakthrough in terms of basic science or investment possibilities. This is because the cost of extracting these surviving stem cells is very high. So is multiplying and reattaching them. The only reason the experiments were even allowed to proceed is that all the cell materials come from the subjects of the procedures. They would not have been allowed if, for example, scientists wanted to use the stem cells from one patient to treat another patient. Nor is it clear to what extent, if any, a company can patent these procedures.

On the other hand, the Italian procedures were most successful when they were combined with the implantation of replacement corneal structures. Those replacement corneas cannot be regenerated from limbal stem cells. In fact, they came from cadavers.

ISCO, however, is now able to grow them in the lab to produce cheaper, safer corneas. ISCO is involved in discussions with various companies to commercialize those parthenogenic corneal structures.

For most patients, who have enough of their own stem cells to regenerate the corneal epithelium, ISCO's corneas are all that are required to recover sight. Eventually, in fact, I suspect that ISCO will also have off-the-shelf limbal stem cells that will regenerate the corneal epithelial too. These cells would be from each of ISCO's cell bank lines. Now being established, it will include 50-100 cell lines that immune match most of the world's population. No other company has this ability to provide inexpensive stem cells for the masses.

Now allow me to debunk some of the rumors currently being spread about ISCO. Normally, as you know, I don't like to dignify these attacks, but I do make exceptions when it's important. I'm doing this, by the way, in a question-and-answer format that board chairman Ken Aldrich was kind enough to answer. The questions deal with some of the unfounded rumors circulating. If these don't concern you, feel free to skip them. Q1. Did ISCO close its financing?



A1. Yes, they did a $10 million financing, and then used $2.5 million as part of a balance sheet cleanup that removed approximately $15 million of 10% preferred stock and still left them with an additional $7.5 million in cash on the balance sheet, in addition to whatever cash was already there.

Q2. Doesn't Socius hold a lot of preferred stock that will be a future burden to ISCO?



A2. No, all of that has been retired as part of the capital restructuring announced in an 8-K filed June 11, 2010. As a result, Socius and its predecessor company, Optimus, hold no preferred shares of ISCO at all.

Q3. Is the company running out of money?



A3. Based on the monthly "burn" rate of about $550,000 for the last 15 months ($562,000 for the last quarter), the proceeds of the company's most recent financing of $7.5 million after the repayment of the outstanding preferred stock of Socius and Optimus would give the company at least 12 months of "runway," even without any additional revenues from operations, licensing or partnerships.



I could go on, but this is pretty long. Next week, I'll have more updates.

For transformational profits,

Patrick Cox

To learn more about Patrick Cox and Breakthrough Technology Alert please click here. © 2010 by Agora Financial, LLC. 808 St. Paul Street, Baltimore, MD 21202. All rights reserved. No part of this report may be reproduced by any means or for any reason without the consent of the publisher. The information contained herein is obtained from sources believed to be reliable; however, its accuracy cannot be guaranteed.

Jeffrey Janus serves as director and senior vice president of operations of new CHI member International Stem Cell Corp. and president and chief executive officer of Lifeline Cell Technology, one of the company’s subsidiaries. International Stem Cell Corp. (ISCO.OB) is a publicly traded stem cell therapy company with research and manufacturing facilities in Oceanside, Calif., and Walkersville, Md. The company’s technology revolves around its discovery of a proprietary and unique class of stem cells called human parthenogenetic stem cells (hpSC). These cells have distinct medical, practical and ethical advantages over embryonic and adult stem cells. They allow immune-matched stem cells and therapeutic cells to be “banked” and available immediately for millions of patients who are in critical need and cannot wait to derive cells from their own bodies. In addition to Lifeline Cell Technology, the company has another subsidiary called Lifeline Skin Care.

Janus is trained in biochemistry and business management and has more than 20 years experience focused on cell-based businesses. He is a member of the team that discovered parthenogenesis and is published in the stem cell field. After joining International Stem Cell Corp., (ISCO) Janus subsequently founded Lifeline Cell Technology to meet a growing need for media and human cells in pharmaceutical drug screening, consumer product testing and basic research at universities and government laboratories and to provide revenue and operational infrastructure for ISCO. The CHI Blog recently caught up with Janus to find out the latest on the company.

Q: How did your company get started? A: We started this company based on the work of Elena Revazova, M.D., Ph.D., a scientist well known in Russia who had a dream of curing diabetes using embryonic stem cells. She came to the United States to work and her talent and expertise in growing human cells was discovered by ISCO’s founders, who decided to form a company around her knowledge and skill. At the time, U.S. President [George W.] Bush was restricting the use of embryonic stem cells on ethical grounds, and there were also patent issues around embryonic stem cells, as there still are. We recognized that the ethical issue was important, but medially the most important problem with stem cell therapy was likely to be immune rejection. We realized we could address these issues by developing the technology called parthenogenesis and mitigate delays from funding and restrictions by working in Russia. So Dr. Revazova went back to Russia, and we set up a collaboration in Moscow to begin her work with parthenogenesis. Today our company has all of the intellectual property rights to parthenogenesis, a very powerful technology. We have also recently brought in Andrey Semechkin, Ph.D. as our CEO. Dr. Semechkin is a well-known scientist in the field of systems analysis and an accomplished businessman.

Q: How does parthenogenesis work? A: It’s the derivation of stem cells from an unfertilized human egg. The ethical issue surrounding work with embryonic stem cells is caused by the fact that embryonic stem cells are derived from a fertilized embryo, which has the potential to be a human being. However, if you do not fertilize the egg and yet you can derive stem cells from it that are functional, you’re not destroying a viable human embryo—and that’s exactly what Dr. Revazova did. We perfected parthenogenesis and brought it back to the United States. As a result, we have been able to overcome the ethical issue surrounding using embryonic stem cells with parthenogenesis.

Q: What are your technology’s other advantages? A: Parthenogenesis makes embryonic stem cells (or what we call parthenogenetic stem cells) that can be immune matched to millions of people. Using embryonic stem cells, the way they are currently made, is sort of like trying to do a bone marrow transplant between one person and another picked at random without making sure you have a match. If someone needs to have a bone marrow transplant, they usually go to brothers or sisters first and try to do an immune match. For a different set of reasons a similar situation exists with blood transfusions, although type O blood can be given to almost everyone. Our cells are similar in that the parthenogenic stem cells can be immune matched to many people, and that’s the unique quality of our cells.

Q: What are the biggest opportunities for your business going forward? A: We are creating a bank of hpSC that are “pluripotent” and carry common immune types that will match a large percent of the U.S. population, and this is a huge opportunity. These will be clinical grade and will be made in our new manufacturing facility located in Oceanside, Calif. Our biggest opportunity is the potential ability of our stem cells to be universally utilized for therapy. Scientists across the world are working on embryonic stem cells and figuring out ways to make therapeutic cells such as liver cells or nerve cells for a whole host of diseases. Eventually these therapies will need a cell or process that will minimize immune rejection. Our cells can be immune matched to millions of persons and are thus a solution for this need. So in a way, much of the work that’s going on right now across the world with embryonic stem cells accrues to our benefit. In addition, we are focused in four distinct areas—diabetes, liver disease, retinal and corneal disease, and nerve disease. We are currently growing cells to cure corneal blindness and have actually grown cornea tissue. We’re working with the University of California, Irvine to grow cells with a retina for macular degeneration. We have grown cells that are very similar to liver cells that are also related to a cell type called beta cells, which may be useful for diabetes. Collaborations with companies and universities present strong opportunities, and we’ve collaborated with Novocell in San Diego to further our work with diabetes, and we’re collaborating with UC San Francisco to test our liver cells derived from our parthenogenic stem cells and with researchers in Germany to study nerve cells generated from our stem cells.

Q: Tell us a little bit about your subsidiaries. A: One unique thing about our company is that we are a research-oriented biotech company that actually has income. One of our subsidiaries, Lifeline Cell Technology, is growing very nicely (with a 150 percent increase in sales over the last year) by selling research products to grow human cells and study human disease. Lifeline has more than 70 products and will be releasing more than a dozen more in 2010. Lifeline Skin Care was created in 2009 based on our discovery that derivatives from our parthenogenetic stem cell technology have proven to be beneficial to human skin. Lifeline Skin Care is developing several products and is beginning early-stage clinical trials with these skin products. We anticipate that these skin care products will help to generate income and fund our continuing stem cell therapeutic research.

Q: What are your company’s greatest accomplishments so far? A. We have successfully created 10 human parthenogenetic stem cell lines, one which carries the most common immune type in the United States and matches over a hundred million persons across the world. We are a fast-growing company with more than 12 scientists working in various areas of therapy and product development. Our stem cells have proven to be able to create cells that may be useful in therapy, including liver-like cells, corneal cells, retinal cells, nerve cells and cell types that may ultimately be useful in the treatment of diabetes. We have set up collaborations with major universities and researchers across the world. The amazing thing about our company is that we have developed into a company that has manufacturing, products, sales, quality control, therapeutic research, and an accounting department in such a short time. We have all the workings of a fully functional product manufacturing and therapeutic research company. It amazes me that we are making sales, whereas most companies our size are basic research and development companies. We know how to make human cells and freeze, store and manipulate them so that they are clinical grade. I think our technology, our knowledge of cell culture and our ability to manufacture are three very strong reasons that we have been successful.

CHI-Advancing California biomedical research and innovation
SOURCE: http://californiahealthcareinstitute.blogspot.com/2010/02/executive-spotlight-jeffrey-janus.html

International Stem Cell Corporation (OTCBB:ISCO), http://www.intlstemcell.com, a California-based biotechnology company focused on therapeutic and research products, congratulates Advanced Cell Technology, Inc. (ACT) on the issuance of its recent patent, U.S. Patent Number 7,736,896, covering a method for producing retinal pigment epithelial cells.

As licensee of the retinal cell technology covered by this ACT patent, ISCO looks forward to building on this discovery, either independently or in collaboration with ACT, with the goal of advancing the search for treatment of such diseases as Macular Degeneration and Retinitis Pigmentosa, leading causes of blindness in adults, both in the US and the World.

In addition to its licensed interest in the ACT patent, ISCO is developing its own proprietary technology for creating and implanting retinal pigment epithelial (RPE) cells that may be usable either in conjunction with its licensed technology from ACT or independently.

'This is just one more example of the remarkable advancement in science toward the treatment of life's more dreaded diseases, and we are proud to be one of the leading pioneers in that effort,' said Kenneth Aldrich, Chairman of ISCO.

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 (hpSCs) from unfertilized oocytes (eggs). hpSCs avoid ethical issues associated with the use or destruction of viable human embryos. ISCO scientists have created the first parthenogenic, homozygous stem cell line that can be a source of therapeutic cells with minimal immune rejection after transplantation into hundreds of millions of individuals of differing sexes, ages and racial groups. This offers the potential to create the first true stem cell bank, UniStemCell^(TM), while avoiding the ethical issue of using fertilized eggs. ISCO also produces and markets specialized cells and growth media for therapeutic research worldwide through its subsidiary Lifeline Cell Technology. 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, and other opportunities for the company and its subsidiary, 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, 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
Brian Lundstrom, President
760-640-6383
bl@intlstemcell.com

International Stem Cell Corporation (OTCBB:ISCO), http://www.intlstemcell.com, a California-based biotechnology company focused on therapeutic and research products, announced today that Charles J. Casamento was elected to the Board of Directors, on June 21, 2010.

Mr. Casamento is currently Executive Director and Principal of The Sage Group, a healthcare advisory group specializing in mergers, acquisitions, and partnerships between biotechnology companies and pharmaceutical companies. During his career, Mr. Casamento has served as a director on the boards of eight public biotechnology/pharmaceutical companies. He was the president and CEO of Osteologix, Inc., a public biopharmaceutical company developing products for treating osteoporosis, from 2004 through 2007. From 1999 through 2004, he served as chairman of the board, president and CEO of Questcor Pharmaceuticals, Inc. Mr. Casamento formerly served as RiboGene, Inc.'s president, CEO and chairman of the board from 1993 through 1999 until it merged with Cypros to form Questcor. He was co-founder, president and CEO of Interneuron Pharmaceuticals, Inc. (Indevus), a biopharmaceutical company, from 1989 until 1993. Mr. Casamento has also held senior management positions at Genzyme Corporation, where he was senior vice president, pharmaceuticals and biochemicals; American Hospital Supply, where he was vice president of business development and strategic planning for the Critical Care Division; Johnson & Johnson, Hoffmann-LaRoche, Inc. and Sandoz Inc. Mr. Casamento also serves on the Boards of Directors of CORTEX Pharmaceuticals, SuperGen, Inc. and VIVUS, Inc. He holds a bachelor's degree in Pharmacy from Fordham University and an M.B.A. from Iona College and was originally licensed to practice pharmacy in the states of New York and New Jersey.

'Mr. Casamento is a vital addition to our Board and brings to International Stem Cell Corporation expertise in areas that will help guide our company through growth, including corporate governance, business development, strategic planning, financing, mergers and acquisitions, product development, clinical trials and corporate and research and development collaboration activities,' said Kenneth Aldrich, Chairman.

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). hpSCs avoid ethical issues associated with the use or destruction of viable human embryos. ISCO scientists have created the first parthenogenic, homozygous stem cell line that can be a source of therapeutic cells with minimal immune rejection after transplantation into hundreds of millions of individuals of differing sexes, ages and racial groups. This offers the potential to create the first true stem cell bank, UniStemCell^(TM), while avoiding the ethical issue of using fertilized eggs. ISCO also produces and markets specialized cells and growth media for therapeutic research worldwide through its subsidiary Lifeline Cell Technology. 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 pertaining to anticipated technological developments and therapeutic applications, and other opportunities for the company and its subsidiary, 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, 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
Brian Lundstrom, President
760-640-6383
bl@intlstemcell.com

OncoMed Has 'Wnt' in its Sails; Bayer Deal Adds $40M Up Front by Jennifer Boggs, Bioworld, June 18, 2010. Excerpts:

[OncoMed's] latest accomplishment is another early stage deal, this time with Bayer Schering Pharma AG, to develop drugs targeting the Wnt signaling pathway. It's an agreement that brings $40 million up front, with the potential for more than $1 billion in future milestones.

.....

The Wnt pathway is believed to be a key target in halting cancer stem cell activity. But only a few other firms - Avalon Pharmaceuticals Inc. (now part of Clinical Data Inc.) and 2008 start-up Wintherix LLC, for example - have entered that space, largely because Wnt is not an easily druggable target.

News release from Bayer: Bayer Schering Pharma and OncoMed Pharmaceuticals Enter Strategic Alliance to Develop Anti-Cancer Stem Cell Therapeutics, June 17, 2010. Excerpt:

Bayer Schering Pharma AG, Germany, and OncoMed Pharmaceuticals, Inc., today announced a global strategic alliance to discover, develop and commercialize novel anti-cancer stem cell therapeutics targeting the Wnt signaling pathway. Cancer stem cells are a subset of tumor cells believed to play a significant role in the establishment, metastasis and recurrence of cancer and agents targeting the Wnt pathway have the potential to be developed as pan-tumor drugs.

Comment: The Bayer-OncoMed strategic alliance has received attention via the social media. See, for example, the results of this FriendFeed search.