One of the most promising alternative sources of human “pluripotent” stem cells is called direct cell reprogramming. It holds out the possibility of producing embryonic-like stem cells, but without destroying, harming, or even involving human embryos in the process.

Reprogramming (also called de-differentiation) proposes to take adult cells from the human body and send each cell's nucleus back to a pluripotent state. In other words, the reprogrammed cells would then be capable of producing any tissue type in the human body—essentially equivalent in versatility to human embryonic stem cells.

Furthermore, these stem cells would be genetically matched to the person who donated the body cells. They could then be used to grow tissues for future use in tissue replacement therapies (everything from regeneration of damaged heart tissue to Parkinson's to spinal chord injury). A perfect genetic match, these tissues would not be rejected by the donor's immune system. Most importantly, there would be no embryo created, destroyed, damaged or used in any way at any point in the process.

One year ago, the journal Cell published research by a Japanese team of researchers lead by Shinya Yamanaka. In that research, Yamanaka reported successes in reprogramming mouse cells by adding four key genes to those cells. His initial research appeared to show that the genes were responsible for sending the adult mouse body cells back to a pluripotent-like state, with qualities similar to mouse embryonic stem cells.

As I wrote last March in this column, Dr. Yamanaka’s findings were like a shot heard round the stem-cell biology world. Almost immediately after his work was published, two additional teams of researchers set out to duplicate and, if possible, exceed Yamanaka’s findings. Those teams were led by Rudolf Jaenisch of the Whitehead Institute, Kathrin Plath of the University of California, Los Angeles, and Konrad Hochedlinger of Massachusetts General Hospital. Dr. Yamanaka as well continued to refine his work, and all had something important to report this summer.

In articles published on June 7 in the journals Nature and Cell-Stem Cell, the three teams gave what most stem-cell scientists would consider definitive proof that Yamanaka’s four genes can, indeed, reprogram mouse cells to a pluripotent state. These “induced pluripotent cells”—(iPCs) as they are now called—have properties virtually indistinguishable from embryo-derived embryonic stem cells.

More details about these studies were revealed a week later at the 5th annual meeting of the International Society for Stem Cell Research held in Cairns, Australia.

The immediate implication of all this is that it should be possible to apply these same techniques to human cells. The question is: how long before we see successful assays at reprogramming human cells? I posed that question to Westchester Institute senior fellow Dr. Markus Grompe who attended the Cairns meetings. While noting that the recent finding are definitely encouraging, Markus was quick to add a cautionary note:

The meeting made it apparent to me that human iPCs equivalent to embryo-derived embryonic stem cells are not going to be a reality soon. Even if human iPCs could be produced today with the same reprogramming methodology that works in mice, we would still have a problem: the current methodology involves inserting viruses containing the reprogramming genes into the chromosomes of the adult cells. There is no easy way to get rid of them after they have done their job of converting the cells from the adult to the pluripotent state. Unfortunately, the continued presence of the reprogramming genes renders the cells likely to become cancerous as shown in several of this summer’s papers.

Last March, Markus speculated that perhaps as many as 50 labs around the world, and upwards of 200 stem cell researchers are currently pursuing cell reprogramming. The Cairns meeting seems to have confirmed this.

So, where does this leave the question of reprogramming? On the one hand, there remain any number of scientific hurdles to the reprogramming of human cells. On the other hand, other scientists I have spoken with express optimism that researchers will not be lacking in motivation and creativity to overcome those hurdles as quickly as possible and make this work with human cells in a manner that is safe and efficient for therapies.

If one day successful, the direct reprogramming of adult cells to the pluripotent state would be the ideal way to produce embryonic-like stem cells for research as well as potential future therapeutic uses. The best part is that, because cell reprogramming holds out the same promise as embryo-destructive “therapeutic cloning”, successful reprogramming of human body cells for therapeutic purposes would render the alleged need for such cloning a moot point.

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