Construction Of Tissue Engineering Liver Unit

Hepatic tissue engineering is a promising approach to developing hepatic tissue suitable for the functional replacement of a failing liver. We try to construct tissue engineering liver unit (TELU) by seeding bone marrow derived mesenchymal stem cells (BDMSC) on the poly DL-lactic-co-glycolic acid (PLGA) scaffold. Firstly, on the basis of isolating and expandingBDMSC, potential differentiations of BDMSC into hepatocytes and blood endothelial cells (EC) were studied and the morphology, marker and function of induced BDMSC were analyzed. Results show that as outerstanding seed cells of tissue engineer, BDMSC induced by suitable condition can be differentiated into hepatocytes and blood endothelial cells (EC) during which Fibrin-gels, Matrigel, basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), fibroblast growth factor 4(FGF-4) and Flt-1 , Flk-1 etc. that expressed by BDMSC after induction maybe supply a proper microenviroment and play an important role. Secondly, construction designation of layers wall, selection of material and optimization of microconstruction were proceeded for the scaffolds of TELU including bifurcated blood vessel scaffold and its outer pack box. Results show that among polymer of PCL/PEG (PU), poly-L-lactate (PLLA), PLGA, chitosan and collagen etc. that were used the most frequently in tissue engineering, PLGA and PU have the best hemocompatibility and cytocompatibility for BDMSC and EC. Diameter and proportion of sodium chloride (NaCl) particulate are respectively responsible for porosity and pore size of PLGA films made by NaCl particulate leaching. BDMSC intergrated with the porous PLGA films made of the 75% (w/w) particulate proportion and 30~50μm pore size not only have the potency of differentiating into functional EC in vitro, but also can be differentiated into EC that extricate themselves from scaffold wall and move chemotacticly and form capillary vessel communicating with blood circulation in vivo. Finally, induced-BDMSC were seeded on bioscaffolds, which were later implanted into abdominal cavity to construct TELU. Results show that pretreated BDMSC seeding on PLGA scaffold could stimulate vasculogenesis and forming TELU possessing blood sinusoid and live hepatocytes. The ways that contract TELU can be used to construct subsidiary fouction unit for hepatic failure, on the basis of which the complete TELU including biliary tract and Kuffer cell maybe be built up in future. The study provides a way and conception for realization of implantable tissue engineering liver.