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

利用体细胞进行器官重建具有重要的临床意义。组织工程领域的最新进展表明，使用胶原基质作为支架有助于组织重建。在这里，我们研究了使用胶原支架移植肝干细胞样(HSL)细胞的效果，HSL是一种先前建立的具有分化潜力的肝上皮细胞系。为此，将HSL细胞与海绵状或胶状的I型胶原基质一起移植到Nagase的蛋白血症大鼠体内。结果，免疫组织化学分析和基因组聚合酶链式反应实验显示移植细胞已经植入。此外，受体大鼠的血清白蛋白水平在移植后被发现比对照组增加了2.5倍。这些发现表明HSL细胞能够在体内分化为有功能的肝细胞，可生物降解的胶原基质可能通过为肝细胞再繁殖提供合适的微环境来增强这种现象。细胞移植用于糖尿病的治疗需要足够数量的β细胞来源。在目前的研究中，我们研究了HSL细胞是否可能成为潜在的β细胞来源。RT-PCR分析表明，丁酸钠和β细胞蛋白诱导的一系列转录因子参与了胰腺内分泌细胞的分化。成人正常肝脏来源的HSL细胞在体外也有向胰腺内分泌细胞分化的潜能。HSL细胞可能是胰岛素依赖型糖尿病细胞移植治疗的潜在β细胞来源之一。

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.