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September 02, 2008
Stem Cell News We Can't Afford to Miss
By Father Thomas Berg *

By Father Thomas Berg *

Buried under news of Phelps's eight gold medals, Russia's renewal of the Cold War,   Sarah Palin's charming debut, and Gustav's perilous approach to New Orleans, there was actually some very important stem cell news at the end of August.

Let's start with news related to cell reprogramming or "induced pluripotent stem" (iPS) cells. I last wrote about iPS cells in December of last year in the column, "The Beginning of the End of the Stem Cell Wars?"  Breakthroughs reported last November in human cell reprogramming in papers published by Shinya Yamanaka of Kyoto University, and by James Thomson of the University of Wisconsin, Madison offered proof of principle that we now have an ethically and scientifically viable alternative to human "therapeutic" cloning (SCNT).

Yamanaka and Thomson, in independent studies, took ordinary human cells (like a skin cell off the tip of your nose) and "reprogrammed" them to become pluripotent cells, cells that could then be coaxed into becoming any other type of cell in the human body. In January, the scientific community was further stunned when Dr. Rudolf Jaenisch of MIT's Whitehead Institute for Biomedical Research reported using the iPS procedure to treat sickle cell anemia in laboratory mice - proof of principle that the iPS procedure, though not ready for direct applications in human patients, might already be used to study and treat animal models of human diseases.

The 'holy grail' of stem cell science continues to be a technique that would allow scientists to create stem cells genetically matched to a sick patient, and then grow and develop these cells into tissues for use in tissue replacement therapies (everything from regenerating damaged heart tissue to treating Parkinson's or spinal-cord injuries). A perfect genetic match, these tissues would not be rejected by the donor's immune system.  The advent of cell reprogramming would now appear to allow scientists to do just that, and to have stolen the prize from the human cloning enterprise - a technique that would conceivably afford the same benefit. We have to recognize, however, that while the 'holy grail' is certainly within reach of the reprogramming scientists, it is not yet in hand.

It continues to be the case that the science of reprogramming still requires substantial refinement before human tissues developed from iPS cells might be used safely in human subjects. Multiple scientific studies show that all pluripotent cells, including human embryonic stem cells (hESCs), form tumors (teratomas) and can convert to cancer cells.  Westchester Institute Senior Fellows Maureen Condic and Markus Grompe have pointed out that the risk of tumor formation may, at this time, be higher in iPSCs than in hESCs because genes inserted for reprogramming remain within in the reprogrammed cells.

The preferable way to reprogram - yet to be accomplished - will be one which eliminates the need to insert genes at all. Ideally, the reprogramming would be achieved by simply soaking the to-be-reprogrammed cells in a cocktail of chemicals which would then jump start the reprogramming process in the cell nuclei.
Fortunately, stem cell scientists are hard at it right now trying to do just that. Papers published in May and early August indicate that they have already identified chemicals that at least facilitate the current iPS techniques.  Dr. Condic, for her part, has also published a paper in which she offers a very complete analysis and comparison of the regulatory issues that will confront iPS-cell derived, human embryonic derived, and cloning derived tissues if and when their corresponding therapeutic applications ever go mainstream.

The most startling news, however, is that scientists might not need stem cells - whether from embryos, from adult tissues or via iPS - at all to develop human tissues for therapies. Scientists appear to be on the cusp of a remarkable new frontier:  the ability to cut out the biological middle-man (the pluripotent stem cell) and go directly from one specific type of adult cell (like a skin cell), transforming it - directly - into another specific and therapeutically useful type of adult cell (like an insulin-producing beta cell).  This new technique, if successful, will allow them to "trans-differentiate" specific cell types directly to other specific cell types without even having to make the cells first pass through a pluripotent state:  no embryonic stem cells necessary, and for that matter, no iPS cells necessary either.

Experts are already calling it biological alchemy. As reported in The Washington Post last Thursday, Harvard's Dr. Doug Melton and team, working with laboratory mice, were able to transform a mouse's specialized pancreatic cells (that normally secrete digestive enzymes) into insulin-producing beta cells - with enormous and potentially life-saving consequences for millions of diabetics. We can expect to be hearing more about trans-differentiation in the coming months as other teams of scientists report in on similar assays. Melton and team, meanwhile, will be pursuing this research with human cells, hot on the trail of an eventual clinical trial.  I currently see no ethical problems with this procedure.

The beauty of it, as with the advent of iPS cells, is that it completely avoids the need to harvest usable cells from human embryos. Once again, the proof appears to be in the proverbial pudding: the best stem cell science is the science that finds creative ways around ethical minefields.

Father Thomas Berg is a priest in the Archdiocese of New York and Professor of Moral Theology at St. Joseph’s Seminary (Dunwoodie).

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