30 October 2014

IPSK – in a couple of days, not in 2-4 weeks

Colonies of induced stem cells can be obtained in 48 hours

NanoNewsNet based on Harvard Stem Cell Institute: HSCI lab explores more efficient ways to generate iPS cellsScientists at the Harvard Stem Cell Institute have found that adding two small molecules to the four classic "Yamanaka factors" makes it possible to obtain mouse induced pluripotent stem cells (iPSCs) in the fastest way known today.

This simple refinement of the recipe for obtaining IPSC, recently published in the journal Nature Methods (Bar-Nur et al., Small molecules facilitate rapid and synchronous iPSC generation), gives colonies in just 48 hours of factor expression – a huge achievement compared to 2-4 weeks of waiting when using other protocols. In addition, the existence of a more effective method for obtaining mouse pluripotent stem cells is proof that a similar result can be achieved when obtaining human iPSCs.

Laboratories have been using the classic recipe for obtaining IPSC by Nobel Laureate Dr. Shinya Yamanaka since its publication in 2006. Four Yamanaka factors – OCT4, KLF4, SOX2, and c-MUS – are sufficient to eliminate the genetic blocks that prevent the reverse transformation of a fully differentiated cell into a stem cell, but this process takes a long time and only in one case out of a hundred ends with success. The low chances of obtaining iPSCs increase the time and financial costs of basic research and have become a source of considerable frustration among those involved in the study of stem cells.

Adding two small molecules to the classical Yamanaka factors
allows you to get colonies of mouse iPSCs in 48 hours.
(Photo: Harvard Stem Cell Institute)

"We asked ourselves why reprogramming mature cells in iPSCs is so inefficient and whether we can improve this process to better understand the underlying mechanisms and for potential therapeutic use," says her supervisor Konrad Hochedlinger, PhD, researcher at the Center for Regenerative Medicine of Massachusetts General Hospital (Massachusetts General Hospital Center for Regenerative Medicine).

Dr. Hochedlinger and his colleagues set out to solve this problem by combining various factors known to facilitate reprogramming and screening that can identify the most successful combination. The best combination turned out to be the classic Yamanaka factors plus two small molecules – ascorbic acid (vitamin C) and CHIR-99021 (an inhibitor of the GSK3-beta signaling pathway involved in intercellular communication).

"We were looking for combinations of factors that would have a synergistic effect," explains Dr. Hochedlinger. "Both of these molecules are known to enhance the formation of iPSCs to some extent, but we found that in combination they increase the efficiency of this process by an order of magnitude."

Now this protocol will help Hochedlinger's laboratory to obtain the iPSCs they need faster to study issues related to the fate and identity of cells. This area of research is directly related to cancer. In addition, the laboratory is interested in studying reprogramming. The researchers want to achieve a change in the fate of cells in a more targeted and therapeutically relevant way. And although preliminary results show that this method of cell processing does not give the same result when obtaining human iPSCs, the development of a similar recipe for the latter will make stem cell-based therapies more realistic.

Portal "Eternal youth" http://vechnayamolodost.ru30.10.2014

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