December 15, 2008
Adult To Pluripotent Stem Cell Conversion Improves

Just a year ago Jamie Thomson's lab at U Wisc showed how to insert 4 genes to convert adult skin cells into pluripotent stem cells that are just as flexible as embryonic stem cells (i.e. they can become all the cell types in the body). Thomson commented more recently that his lab could have done the work 5 years sooner if he'd only believed it was not a hard problem. Well, the technique for doing this has just gotten easier and safer. MIT Whitehead Institute researchers have shown they can use a single virus to deliver 4 genes in a safer way to convert cells into the pluripotent state.

CAMBRIDGE, Mass. (Dec. 15, 2008) Whitehead Institute researchers have greatly simplified the creation of so-called induced pluripotent stem (iPS) cells, cutting the number of viruses used in the reprogramming process from four to one. Scientists hope that these embryonic stem-cell-like cells could eventually be used to treat such ailments as Parkinson's disease and diabetes.

The earliest reprogramming efforts relied on four separate viruses to transfer genes into the cells' DNA--one virus for each reprogramming gene (Oct4, Sox2, c-Myc and Klf4). Once activated, these genes convert the cells from their adult, differentiated status to an embryonic-like state.

However, this method poses significant risks for potential use in humans. The viruses used in reprogramming are associated with cancer because they may insert DNA anywhere in a cell's genome, thereby potentially triggering the expression of cancer-causing genes, or oncogenes. For iPS cells to be employed to treat human diseases, researchers must find safe alternatives to reprogramming with such viruses. This latest technique represents a significant advance in the quest to eliminate the potentially harmful viruses.

Bryce Carey, an MIT graduate student working in the lab of Whitehead Member Rudolf Jaenisch, spearheaded the effort by joining in tandem the four reprogramming genes through the use of bits of DNA that code for polymers known as 2A peptides. Working with others in the lab, he then manufactured a so-called polycistronic virus capable of expressing all four reprogramming genes once it is inserted into the genomes of mature mouse and human cells.

The ability to convert adult cells into pluripotent cells has practical benefits aside from getting around political opposition to human embryonic stem cell work. The ability to create stem cells from adult cells without using a human egg also gets around the limited supply of human eggs as well as making it possible to use the same mitochondria as exist in the donor adult cells. So this opens up the possibility of creating pluripotent stem cells that immunologically and functionally match each person's existing cells.

I am eager to see the development of cell therapies derived from pluripotent stem cells. We all have parts that are wearing out. I see people around me with chronic knee pain, back pain, and other joint and connective tissue problems and think how much better their lives will be once we can repair their worn out knees, spinal disks, elbows, shoulders, and other worn out mechanical parts. I look at people who need to restore their receded gums, replace tissue scarred from burns, or who just have aged and easily scratched skin and think how better off they'd be with some rejuvenated tissues. I think about people who suffer from failing hearts, kidneys, or livers and imagine a future where we can grow replacement organs from stem cells. I want that future to arrive as soon as possible.

Share |      Randall Parker, 2008 December 15 11:15 PM  Biotech Stem Cells

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