Trans-differentiation of a duodenal phenotype on duodenal transplantation of different normal tissues in F344 rats.

The mechanisms regulating stem cell differentiation and self-renewal are largely unknown. Our ultimate goal is to be able to regulate somatic stem cell differentiation and proliferation. In the present study the ability of trans-differentiation was studied when different normal tissue types were transplanted into the duodenum in rats. Pieces of ear (skin), bladder, trachea, diaphragm, pyloric gland, and forestomach from 8-week old GFP-F344 rats were transplanted into the duodenum of F344 rats. Goblet cells with alcian-blue PAS positive mucin and brash border with alkaline phosphatase (ALP) activity appeared in tissues implanted into the duodenum. In addition, GFP-positive duodenal mucosa was observed in all cases by immunohistochemical staining. Moreover, the GFP-positive cells were found to carry the GFP transgene by PCR analysis, indicating that the bladder, trachea, ear (skin), diaphragm, pyloric gland, and forestomach tissues showed a multipotential ability for differentiation. These results indicated that stem cells within tissues have a multipotential ability, trans-differentiating into different organs when transplanted into different environments.

Differentiation of a hepatic phenotype after heterotropic transplantation of heart, kidney, brain, and skin tissues into liver in F344 rats.

While organ-specific stem cells with roles in tissue injury repair have been documented, their pathogenic significance in diseases and the factors potentially responsible for their activation remain largely unclear. In the present study, heart, kidney, brain, and skin samples from F344 transgenic rats carrying the GFP gene were transplanted into normal F344 rat liver one day after an intraperitoneal injection (i.p.) of carbon tetrachloride (CCl(4)) to test their differentiation capacity. The transplantation was carried out by female donors to male recipients, and vice versa. One week after transplantation, GFP antigen-positive cells with phenotypic characteristics of hepatocytes were noted. After two weeks, their extent increased, and at 4 weeks, large areas of strongly GFP-stained cells developed. All recipient livers had GFP antigen-positive hepatocyte cells. PCR analysis coupled with laser capture micro-dissection (LCM) revealed those cells to contain GFP DNA. Thus, our results indicate that tissue stem cells have multipotential ability, differentiating into hepatocytes when transplanted into an injured liver.