Embryonic stem cell research is different from adult stem cell research. Adult stem cells maintain our tissues and organs throughout life, while embryonic stem cells participate in the first building of the tissues of the body. Adult stem cells for all tissues need to be discovered and isolated, and then research carried out to find out how best to use them in treatments to regenerate damaged tissues usually derived from these stem cells. Today in humans we have only isolated blood-forming and brain-forming stem cells. We give therapies with tissues that contain stem cells, usually not purified away from the other cells.
Because the field is so young, lots of mistakes are made. Just five years ago it was popular to think that one kind of stem cell, say a blood-forming stem cell, could turn into another tissue cells, like heart muscle, brain cells, skeletal muscle cells; careful testing with pure blood stem cells showed that notion to be false. Blood stem cells rapidly and robustly regenerate the blood-forming system, but don't regenerate heart or brain cells or muscle cells. Unbelievably, many clinical trials began with that mistaken assumption. So we need to speed up the process to discover the adult tissue stem cells for the tissue that needs to be regenerated-heart, lung, liver, muscle (we have the mouse muscle stem cell and it looks very good; need to get human muscle stem cells), skin (again, mouse skin stem cells are known), kidney, etc.
The promise of embryonic stem cells is that these cells, derived from sperm-egg in vitro fertilizations that were in excess, can in fact make all the kinds of cells in the body. The development of a way to grow them outside the body, and then to allow them to make the other tissue cells, promises to allow us to shortcut finding, say, the stem cells that could end up in the pancreas and make insulin.
There is another kind of stem cell research that could help us a lot, closely related to embryonic stem cells. Normally, when a sperm and an egg fuse, that starts the genetic program to make two kinds of cells in about give days; an outer layer of cells in a ball (called the pre-implantation blastocyst) that will allow the ball to attach to the wall of the uterus to start embryonic development, and a cluster of cells inside the ball that are pluripotent, that is, have many potentials. The inner cells are the ones that can be cultured to make embryonic stem cells. The fused nucleus containing the chromosomes of sperm and egg are instructed by messages within the egg to reprogram them from having on the genes to be sperm or eggs to having on the genes to be pluripotent. Scientists have recapitulated the reprogramming process with mouse cells, starting not with sperm or eggs, but dispensable skin cells. The skin cell chromosomes have on the genes to be skin, and have off the genes to be pluripotent, or be blood cells, or nerve cells, or even sperm or egg cells. Now with mouse cells scientists can put skin cell nuclei with skin cell chromosomes into an egg that had its own chromosomes removed; the egg messages work on the skin cell nucleus to reprogram it almost to pluripotency.
A Japanese group has discovered some of the genes that make messages that reprogram skin cell nuclei. This was also recently confirmed by a group at MIT. We hope this moves fast with human cells. Imagine if we could take a skin cell from someone with a genetic disease, like Lou Gehrig's disease of motor neuron degeneration, or early onset heart attacks because of errors in cholesterol handling; the skin cells have the same genes that led the skin cell donor to have the disease. Now if these could be made pluripotent, we could allow these cells to make Lou Gehrig's disease in a test tube, and find out which parts of the body are damaged when the mutant genes that participate to make the disease are acting. Thanks to the Nobel Prize work of Mario Capecchi and Oliver Smithies, mutant genes in these pluripotent stem cell lines can be accurately and appropriately fixed, and so we could not only figure out which cells are damaged by the mutant genes, but also how fixing the gene fixes the process.
So adult and embryonic stem cell research are very different, and both are very important. If we cancel research in one in favor of the other, we are responsible for the suffering and deaths of people who only have a narrow window of opportunity for a new therapy to help them. In this funding climate, only about 7 to 15 percent of approved grants by the U.S. National Institutes of Health get funded. That means that stem cell researchers like me lose most of our grants, no matter what advances we make, and spend most of our time writing and writing new grant applications. The U.S. government funds embryonic stem cell research only on those cell lines made before Aug. 9, 2001. The U.S. government bans funding of reprogramming research which involves putting a skin cell nucleus into an egg that had its chromosomes removed in order to make a pluripotent stem cell line.
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