Adrenocortical tissue formed by transplantation of undifferentiated cells

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The adrenal cortex consists of morphologically and functionally different three zones, the zona glomerulosa (zG), the zona fasciculata (zF) and the zona reticularis (zR). Recently we discovered another zone (undifferentiated cell zone : zU) between zG and zF. ; cells in the layer are functionally undifferentiated as judged by their inability to express zone-specific steroidogenic enzymes, P450aldo and P45011β, and are thought to be stem cells for adrenocortical cells. In 1999 we successfully established cell-lines exhibiting properties of such adrenocortical stem cells (AcA 101) utilizing mice carrying a temperature-sensitive SV 40T antigen gene. This study was aimed to investigate the mechanisms of differentiation of the undifferentiated adenocortical cells and the formation and maintenance of cortical zones. We obtained the following results in 2 years (2001 and 2002).1. The undifferentiated cell line (AcA 101) expressed P45011β gene at a non-permissive temperature (39℃) of SV40T antigen synergistically with exposure to dibutyryl cAMP and also at the permissive temperature (33℃) with MATRIGEL consisting of laminin and collagen IV.2. A new secretory protein was identified in AcA 101 by subtractive hybridization. The protein contained a secretory signal, EGF-like repeats, and a proteolytically inactive catepsin B-related sequence.3. The mRNA and its encoded protein were detected only in the zU and zG and not in zF., and the protein was designated as adrenocortical zonation factor 1 (AZ-1).4. Interestingly the expression of AZ-1 in adrenocortical cells is inversely correlated with expression of P45011β.5. We have tried to transplant the AcA101 to the kidney of scid mice, but we have not yet succeeded to obtain the regenerated tissues. We are still investigating the conditions for the transplantation of those cells based on the results obtained so fur.