As I summarized in 2007 (JW Dec 28 2007), the great excitement about the potential of embryonic stem cells (ESCs) to treat disease had been tempered by scientific obstacles and ethics questions. No person could be treated by his or her own genetically identical ESCs, because they are long gone. And, using ESCs from a genetically dissimilar embryo would not only impart risk for immune rejection and require immunosuppression but also would raise ethics concerns for some.

As a way around these difficulties, scientists asked an audacious question: What if one could "reprogram" the genes of a specialized adult cell so as to transform it back into a cell with all the potential of an ESC? In 2006, a Japanese team identified a handful of genes that are turned on exclusively in ESCs. In 2007, that Japanese team and several American teams used retroviruses to insert four of those genes into easily obtained skin cells, from mice and humans. Remarkably, this genetic reprogramming transformed the specialized cells into what were called induced pluripotent stem (iPS) cells, which had all the potential of ESCs: They could figuratively turn back the clock and create, for each individual, cells that were equivalent to his or her own long-lost, genetically identical ESCs.

Studies in rodents showed that these iPS cells indeed could fulfill their potential: They effectively cured sickle cell anemia (JW Dec 13 2007) and Parkinson disease in mice. Other researchers created iPS cells from patients with Parkinson disease, Huntington disease, and type 1 diabetes, bringing us one step closer to therapeutic applications for humans (JW Aug 26 2008). Two of the four genes used in creating iPS cells were oncogenes, which, along with the retroviral vector used to deliver them to the cell, imparted risk for iPS cells to become cancerous. However, late in 2008, Japanese and American teams reported that iPS cells could be produced even more simply — without oncogenes or retroviruses (JW Oct 28 2008). Even more remarkably, an American team reported being able to use reprogramming to transform one specialized cell (a pancreatic exocrine cell) into another (a pancreatic β cell) in living mice, thereby curing experimentally produced diabetes, without ever creating iPS cells ex vivo (JW Sep 23 2008).

These discoveries demonstrate that specialized adult cells are much more "plastic" than once imagined and appear to eliminate some of the thornier scientific challenges — as well as the ethics concerns — of stem-cell therapy.

— Anthony L. Komaroff, MD

Published in Journal Watch General Medicine December 29, 2008