DEVELOPMENT OF TRANSPLANTATION REPLACEMENT TREATMENT BY IN UTERO TRANSPLANTATION OF ALLOGENEIC AND XENOGENEIC CELLS INTO FETAL LIVER

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With the development of improved therapies and the significant advances in clinical consequence, organ transplantation has been widely accepted as one of the routine options for treatment of end-stage patients. In contrast, cell transplantation and tissue-engineered constructs have not been accepted by clinicians yet, even though the concept was proposed far early. One of the primary factors restricting the clinical application is the fact that grafts are excluded before they are assimilated in the host. Not only the immune-mediated host reaction, but non-specific elimination mechanism has been considered to play an important role contributing to the graft exclusion. Although it has been imaged that hepatocyte is of well potential to regenerate after injury, liver could hardly recover from most of end-stage disorders like severe hepatitis or cirrhosis. Those patients can be not cured except liver transplantation. Here, allogeneic hepatocyte transplantat, and humanized livestock liver t … More ransplant have gained great attention, as a new therapeutic approach and a new donor-source over severe situation of donor shortage. To across the xenogeneic barrier so that human cells could well fix and proliferate in porcine organ, even in the pig with immunological deficiency, it is necessary to understand the mechanism underlying the host-derived non-specific elimination system and to improve the proliferation ability of graft cells The purpose of this study, therefore, is to investigate how xenogeneic cellular grafts can fix and proliferate in porcine liver.Human-derived hepatic cell line, THLE5b, was used to evaluate its survival ability in mice liver. Adnovirus-based p21 transgene, a molecle known to stop the cell cycle, was transferred into the liver of CB17SCID mice. Partial hepatic resection was completed in the mice that induced p21 transgene over-expressed. Our data indicated that the potential of liver regeneration after partial resection falls down in p21 gene-transferred mice by evaluating the alteration of liver weight and the DNA synthesis. The THLE5b cells, developed as a cell source of human parenchymal hepatocye, proliferate well in vitro, but can only remain its normal morphologic features in the CB17SCID mice. The THLE5b cells, however, start proliferation in partial resected liver of p21 transgene mice. Our study demonstrate that p21 gene-transfer exhibits a negative effect in the liver regeneration after partial liver resection, and it could provide a suitable environment supporting xenogeneic cell proliferation. Less