Development of 2-week method for generating human induced-pluripotent stem cells with 200-fold increase in yield
Fate Therapeutics, Inc. announced today the generation of human induced-pluripotent stem cells (iPSCs) using a combination of small molecules that significantly improves the speed and efficiency of reprogramming. The discoveries, which were made by Sheng Ding, Ph.D. under a research collaboration between Fate Therapeutics and The Scripps Research Institute (TSRI), represent a more than 200-fold improvement in reprogramming efficiency and reduce the reprogramming period to two weeks as compared to methods using only the four reprogramming factors (Oct 3/4, Sox2, Klf4 and c-Myc). This latest advancement has broad implications for the creation of "pharmaceutical grade" iPSCs, reprogrammed cells that can be produced without genetic modification at commercial scale quantity, quality and consistency and continues to bolster the leadership position of Fate Therapeutics in industrialized iPSC technology. The Company is developing minimally invasive techniques for reprogramming and differentiation and has exclusively in-licensed from TSRI and the Whitehead Institute for Biomedical Research a intellectual property portfolio related to iPSC technology dating back to November 2003.
"While recent studies have reported improved methods of reprogramming, those techniques have relied on further genetic manipulation or have not otherwise addressed a fundamental reprogramming challenge - that iPSC generation is still a very slow and inefficient process and results in a heterogeneous population of cells," said Paul Grayson, president & CEO of Fate Therapeutics. "Once again, Dr. Ding and his team are the first group to clear yet another major hurdle required for the widespread commercial use of iPSCs for drug discovery and patient therapies."
The findings of Dr. Ding and his colleagues are published today in the Advanced Online edition of the scientific journal Nature Methods. As compared to using the four reprogramming factors of Oct 3/4, Sox2, Klf4 and c-Myc alone, Dr. Ding discovered a combined chemical approach that dramatically improves (> 200 fold) the generation of iPSCs from human fibroblasts within two weeks of retroviral transduction. The iPSC colonies generated by the Ding team using a 3-compound cocktail could be stably expanded over the long term (20+ passages), closely resembled human embryonic stem cells in terms of morphology and pluripotency marker expression and could be differentiated into derivatives of all the three germ layers both in vitro and in vivo.