Early events in the formation of a tissue structure from dispersed bovine adrenocortical cells following transplantation into scid mice

Abstract.

The early events that follow the transplantation of dispersed bovine adrenocortical cells into scid mice were investigated. We introduced adrenocortical cells into a small cylinder inserted beneath the kidney capsule, where they form a tissue structure that becomes vascularized and secretes steroids that replace those from the animal's own adrenal glands, which are removed during the transplantation surgery. We studied cell proliferation, cell survival, apoptosis, and the role of p21^{WAF1/CIP1/SDI1} over the first 6 days following transplantation. Additionally we examined the invasion of the tissue by host macrophages and endothelial cells. The data show that there is healthy survival of most of the transplanted cells, and that this is related to their position in the cell transplantation cylinder. In the layer of cells that was adjacent to the kidney parenchyma there was a higher rate of cell proliferation and a lower rate of apoptosis than in cells that were located in the upper part of the cylinder. In the lower layer cells were more likely to have nuclear p21, and macrophages and endothelial cells were observed only in this region. Cells that incorporated bromodeoxyuridine administered to animals 2 or 4 days following transplantation were not more likely than other cells to be undergoing a second division when the animals were killed at 6 days, suggesting that proliferation in the lower layer is not confined to a small subpopulation of cells. Among different animals, the extent to which the spaces between the transplanted cells became lined by host endothelial cells was correlated with higher levels of proliferation and nuclear p21, suggesting that vascularization is the critical step for the continued survival and proliferation of the transplant. The present experiments show that bovine adrenocortical cells transplanted into scid mice form a useful model for the study of tissue formation from dispersed cells and the interaction of the transplanted cells with the host.