International Stem Cell Corporation (ISCO), together with colleagues from ViaCyte (formerly Novocell) announced the successful derivation from its human parthenogenetic stem cells (hpSCs) of enriched cultures of definitive endoderm (DE). DE can be further developed into pancreas or liver cells. These new results create a platform for the development by ISCO of therapeutic products that have great potential to overcome the problem of rejection of transplanted cells by the patient’s own immune system.

The results are described in a new article that will appear in Differentiation, the official journal of the International Society of Differentiation, published by Elsevier. The article concludes that, “Creation of the definitive endoderm lineages from hpSC represents the critical first step toward the development of hpSC-based cellular therapies for diseases of the liver or pancreas”.

The article also describes improvement in an earlier published differentiation protocol. This new method extends ISCO’s portfolio of intellectual property, demonstrating for the first time that the pre-treatment of undifferentiated cells by trichostatin A (TSA) significantly improves the efficacy of the differentiation procedure.

“This work represents a step forward in our ability to direct the differentiation of hpSCs to cell populations of sufficient purity for their eventual use to produce commercially viable populations of endoderm lineage cells such as liver and pancreas”, said Nikolay Turovets, PhD, ISCO’s director of research and therapeutic development, and the paper’s co-author.

The published work was carried out in collaboration with scientists from ViaCyte, a leader in the direct differentiation of pluripotent stem cells toward definitive endoderm and pancreatic cells. The ViaCyte team was led by Dr. Baetge, currently director of the Nestlé Institute of Health Sciences S.A., Lausanne, Switzerland, and Dr. D'Amour, ViaCyte’s director of Stem Cell Biology; both pioneers in the development of endoderm from human embryonic stem cells.

Andrey Semechkin, PhD, ISCO’s CEO and the paper’s co-author said: “The fact that hpSC could be differentiated into progenitors of pancreatic and liver cells has now become a proven scientific fact. This data establishes hpSCs as a useful source of starting material in stem-cell based technologies and demonstrates excellent progress in therapeutic research.”

According to earlier published scientific data, the most efficient method for deriving pancreatic and liver cells from human pluripotent stem cells is a method of direct differentiation that utilizes treatment of the stem cell cultures by specific signals directing differentiation toward particular lineages. Therefore it is extremely important that stem cells used for the differentiation process are able to respond to such signaling. Dr. Semechkin commented, “In this published paper we report for the first time that hpSCs can respond to well characterized differentiation signals. Moreover, we demonstrate that these unique cells respond to similar signalling factors and demonstrate gene expression dynamics and transitions that simulate properties of DE differentiation during vertebrate development and closely follow differentiation of human embryonic stem cells to DE. These data are extremely important as they demonstrate that hpSCs have therapeutic potential; however, parthenogenetic stem cells have an additional benefit of superior immune-matching capabilities and don’t pose the same ethical questions associated with embryonic stem cells."

International Stem Cell Corporation is a California-based biotechnology company focused on the therapeutic applications of human parthenogenetic stem cells and the development and commercialization of cell-based research and cosmetic 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.