Fate Therapeutics, Inc. claims to have significantly improved the speed and efficiency of reprogramming adult cells into human induced-pluripotent stem cells (iPSCs) using a combination of small molecules.
The discovery, which was made by Sheng Ding, Ph.D. under a research collaboration between Fate Therapeutics and The Scripps Research Institute (TSRI), represents a more than 200-fold improvement in reprogramming efficiency and reduces 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 advancement has implications for the creation of "pharmaceutical grade" iPSCs, reprogrammed cells that can be produced without genetic modification at commercial scale quantity, quality and consistency.
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 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.
"Once we achieved reprogramming with cell-penetrating proteins, we targeted certain biological pathways that might improve speed and efficiency so as to enable the commercial scale production of patient-specific iPSCs for medical use," said Dr. Ding, associate professor of TSRI and scientific founder of Fate Therapeutics. "When combined with non-viral, non-DNA based methods for iPSC generation, we believe these discoveries create a powerful platform for safer, more efficient reprogramming of human somatic cells."
Earlier this year Dr. Ding and his team became the first group to generate iPSCs using non-viral, non-DNA based reprogramming methods. Instead of inserting the reprogramming factors of Oct 3/4, Sox2, Klf4 and c-Myc with DNA-based methods, such as viruses or plasmids, the scientists engineered and used recombinant proteins to reprogram cells without genetic modifications. The scientists found that those reprogrammed embryonic-like cells – dubbed "protein -induced pluripotent stem cells" or "piPSCs" – from fibroblasts behave indistinguishably from classic embryonic stem cells in their molecular and functional features, including differentiation into various cell types, such as beating cardiac muscle cells, neurons, and pancreatic cells.
Adapted from the Fate Therapeutics announcement via EurekAlert.
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