The Enormous Potential Value of Stem Cell Research

Stem cell research is a step to be taken toward the improvement of transplantation therapy and toward lengthening a person's life.We will postpone discussion of life-extension, noting here the relevance to transplantation medicine. Specifically, rejuvenation through transplantation of tissue grown in a laboratory from stem cells would be of enormous value for cardiomyocytes to renew heart muscle to prevent congestive heart failure; replacement of hematopoietic stem cells for producing healthy blood in bone marrow to resist infection by the human immunodeficitent virus and to treat AIDS and possibly sickle cell anemia; cultivating endothelial cells to reline blood vessels as treatment for atherosclerosis, angina, and stroke due to arterial insufficiency; rejuvenating islet cells in the pancreas to produce natural insulin to fight diabetes; renewal of neurons in the brain to treat Parkinson's disease and victims of stroke; fibroblast and keratinocyte cells to heal skin in the treatment of burns; and chondrocytes or cartilage cells to treat osteoarthritis or rheumatoid arthritis.

The trick will be to discover just what turns which genes on and off. Once scientists have learned how to trigger gene expression, they can apply it to pluripotent stem cells and direct the growth of selected bodily tissue. Particular organs could be grown in culture. Heart tissue or entire organs such as the pancreas or liver could be grown in the laboratory. These would be healthy rejuvenating organs ready for transplantation.

In order to transplant the laboratory grown organs, however, we need to override our immune system in order to avoid organ rejection. Two scenarios lie before us. One would be to create a 'universal donor' cell that would be compatible with any organ recipient. The task here would be to disrupt or alter the genes within the cell responsible for the proteins on the cell's outer surface that label them as foreign to the recipient's immune system. This approach would be difficult. It would involve disrupting genes within the same DNA in which we are trying to express certain other genes. Exposing such cells to harsh conditions with rounds of different drugs may damage more than just the targeted surface proteins.

A preferable second scenario would be to make cells that are genetically compatible (histocompatible) with the organ recipient--that is, to make cells with an identical genotype. If the organ genotype matches that of the recipient, no immune system rejection will take place.

Enter cloning--that is, somatic cell nuclear transfer. We can imagine the following scenario for customizing organ growth and transplantation. We could begin with an enucleated human oocyte--that is, we could begin with an egg with the DNA nucleus removed. Via somatic nuclear transplantation--cloning--we could insert the DNA nucleus of the future transplant recipient. We could then turn on selected genes--that is, we could cause the stem cell to differentiate into cardiomyocytes to produce heart tissue. The heart tissue could be grown ex vivo, outside the body, and then through surgery placed within the recipient. Because the implanted heart tissue has the same genetic code as the recipient, no rejection would occur. This is in part the Dolly scenario. It differs in part because it grows only organ tissue and not an entire fetus.

Another variant on the second scenario that distinguishes it from Dolly would be one that eliminates the use of the oocyte. Instead of an oocyte, the recipient's DNA nucleus might be placed within a non-egg cell. The goal would be to accomplish laboratory organ growth in a stem cell that is not an egg. To accomplish this, we need further research on cytoplasm's role in gene expression.

What is there in the cytoplasm that programs the DNA? Could we discover this? If so, we could begin not with an oocyte but rather with an hES cell. We could enucleate a non-egg stem cell and insert the specific DNA nucleus, then reprogram the cytoplasm to cause the desired differentiation.

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