Peter J. Hornsby, Ph. D.
Baylor College of Medicine

Cell Transplantation Models for Gene Action in Human Aging.

The overall aim of this grant is to provide new methods for the study of gene action in human aging, using cell transplantation techniques applied to human adrenocortical cells. Prior to beginning this grant, we had established methods for genetic modification of bovine adrenocortical cells and for examining the function of genetically modified cells after they have been introduced into scid mice. At the beginning of this grant period we were studying the behavior of genetically modified human adrenocortical cells after transplantation in the scid mouse model. Genetically modified human adrenocortical cells proved to be more fragile than genetically modified bovine cells when subjected to cell transplantation. To help solve this problem we have been making chimeric transplants in which normal bovine adrenocortical cells are mixed together with genetically modified human adrenocortical cells. The latter have been marked with a retrovirally encoded gene, such as green fluorescent protein or SV40 T antigen (the latter can readily be detected in the nucleus with a specific antibody). To our surprise, we have found that human adrenocortical cells selectively die in these chimeric transplants, suggesting that the loss of the cells is cell autonomous, and not due to the tissue microenvironment, since the remaining bovine adrenocortical cells form a normal tissue structure. However one very interesting finding is that telomerized human cells remain longer in the transplant than other genetically modified cells. This raises the possibility that telomerase may have an anti-apoptotic effect in human cells, apart from its role in telomere length maintenance.

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