The first research reporting the productions of induced pluripotent stem cells (iPSCs) was announced five years ago. Since then, the field has made significant progress, encouraging high hopes that iPSCs could be so similar to embryonic stem cells (ESCs) that they could eventually replace ESCs in research and therapeutic applications.
However, as with almost any new technology, there have been various problems along the way. These include incomplete reproduction of all important characteristics of ESCs, alterations of cell DNA that might cause cancer, and susceptibility of iPSCs to rejection by the immune system even of the donor of the reprogrammed cells.
Further progress depends on being able to deal with these problems. In addition, depending on the method used to produce iPSCs, the process may be too slow and inefficient for practical use. The latest research demonstrates what appears to be an effective technique to significantly improve speed and efficiency of reprogramming.
Researchers from the Wellcome Trust Sanger Institute have today (10/10/2011) announced a new technique to reprogramme human cells, such as skin cells, into stem cells. Their process increases the efficiency of cell reprogramming by one hundred-fold and generates cells of a higher quality at a faster rate.
Until now cells have been reprogrammed using four specific regulatory proteins. By adding two further regulatory factors, Liu and co-workers brought about a dramatic improvement in the efficiency of reprogramming and the robustness of stem cell development. The new streamlined process produces cells that can grow more easily.
Most approaches to making iPSCs depend on increasing the expression levels of four transcription factors: Oct4, Sox2, Klf4, and c-Myc (or closely related factors). These transcription factors in turn cause the expression of many other genes that bring about the pluripotency characteristic of ESCs, i. e. their ability to develop into any other cell type.
Oct4, in particular, seems to have an especially important role. The new research shows that retinoic acid (RA), a metabolite of vitamin A that is important in early embryonic development, positively affects expression of Oct4. And even better, when RA signaling is enhanced by stimulating expression of RA receptors (RARs), production of iPSCs is much more rapid and efficient. Two nuclear receptors involved in RA signaling, Rarg and Lrh-1, were especially important.