| Bone marrow stem cells (BMSCs) possess multi-differentiate potentials; they can differentiate into cells of blood, muscle, neural, skin, pancreas and liver, etc. in appropriate micro-environment. It has been proposed that this 'trans-tissue', even 'trans-germ layer' differentiation be named as 'plasticity' or transdifferentiation, which brings us the hope of stem cell therapy for end-stage liver diseases and supplies ideal seed cells for bio-artificial liver, hepatocyte transplantation, and liver tissue engineering with BMSCs. However, there are lots of doubts and uncertainties in the influencing factors and control agents of effectively inducing stem cell differentiation, the efficiency of stem cells' differentiation into hepatocytes, differentiated cells' life-span and functional state, etc., and there are many obstacles in application of them clinically. In this study, we established the biological model of differentiation of human/rat bone marrow/umbilical cord blood derived adult stem cells into hepatocytes in vivo and in vitro for going deep into the mechanism of stem cell plasticity, and introduced gene engineering, cell engineering and material science into stem cell biology. It was showed that bone marrow and cord blood stem cells could differentiate into mature and functional hepatocytes, which was determined by the feasible microenvironment provided by injury, special growth factors combination, together with hepatic nonparenchymal cells. Magnetic targeting therapy of BMSCs could enhance the enrichment of stem cells in liver. Mature hepatocyte, hgf-transgenic liver nonparenchymal cells and/or BMSCs co-encapsulated transplantation improved acute liver failure rats' function effectively. The studies offered a theoretical and technical foundation of gene and stern cell engineering-based regenerative medicine for end-stage liver diseases. |
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