Regenerative Medicine - How Induced Pluripotent Stem Cells Work

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