Only two years ago, in the fall of 2007, two teams of researchers reported the successful reprogramming of an adult human cell back to an original state of pluripotency.
Such a reprogrammed cell - termed an induced pluripotent stem cell (iPS cell) - has the ability to differentiate into any type of cell.
iPS cells have the ability to become specialized cells such as pancreatic islet cells which produce insulin, intestinal lining cells which produce digestive enzymes, kidney cells, heart cells, nerve cells, skin cells, and muscle, ligament, cartilage, and bone cells.
Under the right conditions iPS cells could produce specific cells, tissues, and organs for use in treating disease and/or transplantation.
Reprogramming adult cells opens up entire new fields of medical research.
If iPS cells are found to be similar to embryonic stem cells (ESCs), the possibility of reprogramming will significantly impact the controversy surrounding ESC research.
Reprogramming uses adult cells rather than ESCs, and much of regenerative medicine might be able to proceed without the necessity for destruction of embryos.
The two teams, led by Dr.
Shinya Yamanaka at Kyoto University in Japan and Dr.
James Thomson at the University of Wisconsin, used similar methods to reprogram adult human skin cells.
Years of research led to the identification of several specific genes which would induce a cell to return to a pluripotent state.
Dr.
Yamanaka initially worked with a set of 24 genes, attempting to identify the most effective candidates.
Research led to the selection of a group of four genes - Sox2, c-Myc, Oct-4, and Klf4.
These genes were inserted into virus particles and the virus was used to transfect adult skin cells.
Activation of these genes within the adult skin cell leads to the expression of specific transcription factors.
These proteins activate other genes within the skin cell which cause the cell to return to a pluripotent state.
The breakthrough was front-page news in The New York Times, but many aspects of the procedure needed to refined and revised.
Use of a virus to introduce the transforming genes is problematic.
Viral genetic material is transfected as well, and there may be many unanticipated results such as causing the cell to become cancerous.
Viral RNA or DNA would become a permanent part of the cell line - any cells, tissues, or organs derived from the original iPS cell would contain that viral genetic information.
Using viral delivery systems on a large scale would result in transformation of the human genetic heritage, with unforeseen and probably disastrous consequences.
Research has been ongoing since 2007 to derive non-viral methods of introducing the transformative genes.
Dr.
Rudolf Jaenisch, at the Whitehead Institute for Biomedical Research in Cambridge, MA, leads one of the teams working worldwide to solve these challenges.
His team recently identified a small protein molecule which is able to replace Klf4, one of the genes used to reprogram adult cells.
If all the genes can be successfully replaced by small molecules, a viral delivery system would not be necessary.
Such a development would fully launch the field of regenerative medicine.