June 1, 2014 (Vol. 34, No. 11)

Therapeutic Stem Cells from Unfertilized Eggs Sidestep Ethical Issues, Avoid Immune Rejection

Committed to regenerative medicine but fundamentally opposed to the use of embryonic stem cells, the founders of International Stem Cell Corporation (ISCO) created a new class of pluripotent human stem cells. Now, eight years later, this work has resulted in UniStemCell™, the largest privately owned pluripotent stem cell bank.

It is populated with a number of genetically diverse, pluripotent stem cells developed through parthenogenesis, which creates stem cells from unfertilized eggs (oocytes) rather than embryos. These stem cells bypass the ethical concerns of embryonic stem cells and may significantly reduce the risk of being rejected by the immune system.

“We can make these cells in a couple different ways, which is unique to our platform,” says the company’s executive vice president, John Simon Craw, Ph.D. Options are to create either human leukocyte antigen (HLA) heterozygous human parthenogenetic stem cells (hpSCs) that are a perfect match with the egg donor, or to create HLA homozygous hpSCs, which match to anyone carrying that haplotype. One stem cell line in the bank matches over 50 million people. This makes it possible for a single cell line to treat millions of genetically disparate patients.

“These stem cells are as powerful as other types of stem cells, but without the ethical controversies of creating, then destroying, embryos,” Dr. Craw explains.

As Ruslan Semechkin, Ph.D., CSO, points out, “Our stem cells are as genetically stable as embryonic stem cells and probably more stable than induced pluripotent stem cells (iPSCs).” Moreover, hpSCs are truly self-renewing, essentially immortal, and can maintain their genetic stability over hundreds of cell divisions. In contrast, iPSCs are very difficult to create and are somewhat unstable genetically, making them useful for research, but less valuable for therapeutic use.

Stained neural stem cells (NSCs) derived from ISCO’s human parthenogenetic stem cells. NSCs are used to treat Parkinson’s disease.

Projects Are Preclinical

ISCO’s lead therapeutic candidate targets Parkinson’s disease. Dr. Semechkin says he expects to complete IND-enabling studies this year. The company had a pre-IND meeting with the FDA in February, and currently is working to complete the necessary tumorigenicity, toxicology, and tolerability studies.

ISCO’s first clinical product will be human parthenogenetic neural stem cells (hPNSCs)—self-renewing multipotent cells that differentiate into key cells in the central nervous system. ISCO literature says they are “differentiating into dopaminergic neurons and expressing specific neurotropic factors to protect the nigrostriatal system of the brain.” Along with expressing brain-cell-protecting neurotrophic factors that prevent further damage, the cells can engraft and produce the dopamine necessary to prevent the symptoms of Parkinson’s disease.

Importantly, unlike other neuronal cells, hPNSCs can be cryopreserved and delivered to clinical sites in a frozen state.  Clinics thaw the cells when needed, performing the quality control and viability tests just before implantation.

“Additionally, a number of other indications including stroke, traumatic brain injury, and amyotrophic lateral sclerosis can also be treated with neural stem cells, making it a very attractive product from a commercial perspective,” Dr. Craw asserts.

While this will be the first therapeutic to market, the company also has 128 patents and cross-licenses, with another 90 patents pending. Those patents and licenses span 30 patent families, covering specific hpSC lines as well as production and differentiation methodologies for research, therapeutic, and commercial applications.

Another program using ISCO’s technologies creates a human cornea from stem cells, enabling corneal tissue implants. Because corneal tissue is made of multiple cell types and structures, “This is quite an achievement,” Dr. Craw says. The company plans to commercialize this product in India through Insight Bioventures.

“The greatest need for corneal tissue is in India and China, where healthcare systems are not well developed and eye-banking is rare,” he elaborates. “The Indian population also has a slight genetic predisposition to a particular corneal disease.” In the United States, because there is an excellent network of eye banks and limited cultural resistance to the organ donation, there is no significant market for this product.

ISCO also has a program to create liver cells using its stem cell platform. “In some inherited liver diseases, such as Crigler-Najjar Syndrome, the liver lacks the ability to create a particular enzyme. In such cases, liver transplants and hepatic cell transplants have been useful,” notes Dr. Craw. “However, liver cells are not cryopreservable and do not last more than a few hours outside the body. Consequently, the major problem is obtaining sufficient donated liver cells.”

ISCO is optimistic about its “liver-like” cells. The company says they perform as well as those from donated liver cells in animal models of liver disease.

Stained clusters of neurons differentiated from NSCs. These neurons produce the dopamine that is absent in Parkinson’s disease patients.

Business Model

ISCO, which is publicly traded on the OCTQB exchange, has a multifaceted business model. It includes the UniStemCell bank, development and partnering options for therapeutic cellular products, and two commercial subsidiaries selling biomedical research and dermatological products. Several initiatives are already providing revenue.

Its Lifeline Skin Care division—“a stem cell skin care company,” Dr. Craw says—in 2013 reported sales increases of 46% from the previous year, turning a profit. Lifeline Skin Care markets and sells its products in the United States through dermatologists’ offices and medical spas.

Internationally, the company uses a network of distributors. In April, the company signed an agreement with Mexican distributor Grupo Venta Internacional to sell products to physicians in Mexico, Latin America’s second-largest market for aesthetic and reconstructive products.

ISCO’s second subsidiary, Lifeline Cell Technology, sells primary human cells and optimized cell culture media. In 2013, it increased sales by 24% compared to 2012. “The two Lifeline divisions gives our investors actual revenues. We think this offsets some of the risk that investors associate with something as new and revolutionary as regenerative medicine,” Dr. Craw contends.

The hpSCs already are used by The Scripps Research Institute, the Sanford-Burnham Medical Center, and other academic collaborators. But ISCO will not content itself with providing research tools, Dr. Craw makes clear: “Once we have completed the early-stage clinical trials, our goal is to find partners to facilitate larger-scale clinical trials, bring these products to market, and help millions of people who have very little hope at the moment.”

International Stem Cell Corporation (ISCO)

Location: 5950 Priestly Drive, Carlsbad, CA 92008
Phone: (760) 940-6383
Website: www.internationalstemcell.com
Principal: Andrew Semechkin, Ph.D., CEO and board co-chairperson
Number of Employees: 38
Focus: ISCO, a regenerative medicine company, develops parthenogenesis-based stem cells. It focuses on preclinical therapeutics for neurological diseases (such as Parkinson’s) as well as eye and liver diseases.

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