Search for facto s that induce transdifferentiation from liver stem cell to epitheial cells of digestive gland and development with tissue engineering

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Organ restitution using somatic stem cells is of great clinical interest. Recent advances in the field of tissue engineering have demonstrated that the use of collagen matrices as scaffolds facilitates tissue reconstruction. Here we have examined the efficacy of transplantation of hepatic stem-like (HSL) cells, a previously established liver epithelial cell line with a potential for differentiation, using collagen scaffolds. To this end, HSL cells were transplanted into Nagase's analbuminemic rat with spongy or gelatinous type I collagen matrices. Consequently, immunohistochemical analyses and genomic PCR experiments revealed engraftment of the transplanted cells. Furthermore, the levels of serum albumin in recipient rats were found to increase up to 2.5 fold relative to controls after transplantation. These findings suggest that HSL cells are able to differentiate into functional hepatocytes in vivo, and that biodegradable collagen matrices may enhance this phenomenon by providing an appropriate microenvironment for hepatocytic repopulation.To apply cell transplantation for treatment of diabetes mellitus, a sufficient number of beta-cell sources are required. In the present study, we examined whether HSL cells could be a potential beta-cell source. RT-PCR analysis revealed that a series of transcriptional factors involved in differentiation of pancreatic endocrine cells was induced by the treatment with sodium butyrate and betacellulin. HSL cells obtained from adult normal liver also have the potential to differentiate into pancreatic endocrine cells in vitro. HSL cells may be one of the potential beta-cell sources for cell transplant therapy for insulin-dependent diabetes.