Hepatocyte transplantation

Hepatocyte transplantation is being explored as an alternative to whole-organ transplantation. In addition, gene transfer therapy is being developed for familial hypercholesterolemia. A non-invasive method to serially assess the metabolic status and proliferation of hepa-tocytes transferred as treatment for end-stage liver disease or genetic... 

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Bilir, B.M., Guinette, D., Karrer, F., Kumpe, D.A., Krysl, J., Stephens, J., McGavran, L., Ostrowska, A., Durham, X Hepatocyte transplantation in acute hver failure. Liver Transplant. 2000 6 32-40... 

Habibullah, CM., Syed, I.H., Qamar, A., Taher-Uz, Z. Human fetal hepatocyte transplantation in patients with fulminant hepatic failure. Transplantation 1994 58 951-952... 

Snndback, C.A. Vacant , J.P. Alternatives to hver transplantation From hepatocyte transplantation to tissue-engineered organs. Gastroenterology 2000 118 438 -442... 

Wang, X., Andersson, R. Hepatocyte transplantation a potential treatment for acute hver failure. Scand. J. Gastroenterol. 1995 30 193-200... 

Fig. 15. Histologic appearance of hepatocytes transplanted between syngenic Fischer rats 9 weeks after transplantation into the mesentery using the PGA mesh. Hepatocytes are located in small islands (arrows) predominantly at the interface of the host tissue. Connective tissue surrounding the polymer fibrils can be seen in the lower right [from Cima el al. (66)].

Nakamura J, Okamoto T, Schumacher IK, et al. (1997). Treatment of surgically induced acute liver failure by transplantation of conditionally immortalized hepatocytes. Transplant. 63 1541-1547. 

D. Hepatocyte transplantation Our initial polymer design was that of a small wafer of biodegradable polyanhydride. Hepatocytes were seeded in a monolayer onto the wafer in culture and then placed into the recipient animal while on the disc. We found that the cell number and cell density were inadequate for reliable successful engraftment when using this polymer design. Our preliminary studies indicated that for adequate hepatic function, we would need to implant at least 10% of the number of cells found in a normal liver(28). We... 

These findings have led us to conclude that the matrix to which the cells are attached in vitro would be one of the most important variables of our system as we continued to search for the ideal polymer matrix. The hepatocyte-polymer scaffolds, created as described above, were tlaen implanted into the omentum, the interscapular fat pad, or the mesentery of the recipient animal for varying periods of time. We avoided surgical trauma as much as possible, because any fibrin clot or hematoma formation would decrease the ability to nourish the cells by diffusion. The rat was used as the animal model for hepatocyte transplantation, because there existed several models of metabolic deficiency states representative of human liver disease. 

We have observed decreases in serum bilirubin levels of up to 50% and appearance of conjugated bilirubin products in the native bile up to nine weeks post transplantation, indicating metabolic activity in the transplanted cells. While promising, these results were difficult to consistently reproduce, and successful hepatocyte transplantation was limited by cell injury and hypoxia at the time of transplantation. Cell death prevented consistently adequate cell mass engraftment to replace function. 

Mito M, Ebata H, Kusano M, Onishi T, Saito T and Sakaamoto S. Morphology and function of isolated hepatocytes transplanted into rat spleen. 1979 Transplantation 28 499-505. 

Jirtle RL, Biles C, and Michalopoulos G. Morphologic and histochemical analysis of hepatocytes transplanted into syngeneic hosts. 1980 Amer. J Path. 101 115-26. 

Stein JE, Gilbert JC, Hansen LK, Schloo B, Ingber D, Vacant JP. Hepatocyte transplantation into prevascularized porous matrices. J Ped Surg 1991 (Abstr.)... 

Mooney D J, Park S, Kaufmann P, Sano K, McNamara K, Vacanti J P and Langer R, Biodegradable sponges for hepatocyte transplantation , J. Biomed. Mater. Res.,... 

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