Transplantation liver cell

In the process of regeneration, irreversibly damaged or surgically removed liver tissue is replaced as far as possible by new growth. The regeneration of the liver (s. p. 5 ) is a most important process in (7.) overcoming necrosis, (2.) determining the course of a liver disease, (i.) liver resection, (4.) partial liver transplantation, and (5.) liver cell transplantation. (29)... 

Brooks A, Guilmette R, Hahn F, et al. 1986. Uptake and clearance of plutonium-238 from liver cells transplanted into fat pads of F344 rats. Int J Radiat Biol Relat Stud Phys Chem Med 50 631- 640. 

Moscioni AD, Roy-Chowdhury J, Barbaour R, Brown LL, Rot-Chowdhury N, Compeetiello PL, and Demetriou AA. Human liver cell transplantation prolonged function in athymic Gunn and athymic analbumenemic rats. 1989 Gastroent. 96 1546-1551. 

Cellular therapies in transplantation and cancer are based on specific cells separated or sorted from human blood, bone marrow, or cord blood by means of their specific cell surface markers or cell differentiation antigens, e.g., CD3, CD4, CD8, CD 14, CD 19, and CD34. For example, the CD34+ stem cells, especially those derived from human embryos, have the capacity to differentiate in culture to generate different somatic cells, e.g., liver cells, heart cells, neurons, etc. This exploding field of research is now termed regenerative medicine. 

A number of small biotechnology companies and academic research teams are working on these problems. However, worries about the pig RNA viruses have cooled enthusiasm for xenotransplantation. Although some laboratory work continues, there appear to be no immediate human xenotransplant studies on the horizon. Some researchers have, however, proposed using pig liver cells in a device kept outside the body to help remove toxins from the blood of patients whose liver has failed, to help the patients survive while they wait for a human liver transplant. 

T.A. Ageev et al, studied efficiency of the scheme cyclophosphane-vincristine-prednisolone for the therapy of transplanted lymphosarcoma, and found that administration of Enterosgel to animals decreased liver cell damage and concentration... 

Rhim, J., Sandgren, E., Degen, J., Palmiter, R., and Brinster, R. Replacement of diseased mouse liver by hepatic cell transplantation. Science 263, 1149. 1994. Weglarz, T., Degen, J., and Sandgren, E. Hepatocyte transplantation into diseased mouse liver Kinetics of parenchymal repopulation and identification of the proliferative capacity of tetraploid and ostaploid hepatocytes. Am J. Pathol. 157, 1963, 2000. 

Yarmush, M., Dunn, J., and Tompkins, R. Assessment of artificial liver support technology. Cell Transplant. 1,323,1992. 

Wake, M.C., Patrick, C.W and Mikos, A.G., Pore morphology effects on the fibrovas-cular tissue growth in porous polymer substrates. Cell Transplant. 3, 339,1994. Gion, T, Shimada, M., Shirada M., et al. Evaluation of a hybrid artificial liver using a polyurethane foam packed-bed culture system in dogs. Journal of Surgical Research 82, 132-136 1999. 

Despite these failures, the need still exists for alternative liver therapies. Several new techniques including cell transplantation, tissue-engineered constructs, and extra- and paracorporeal devices seek to relieve some of the demands placed on a compromised liver. Liver assist devices allow the liver to regenerate its function by removing some of the demands. Bridge-to-transplant devices seek to maintain patients until suitable donors are available. Some therapies seek to remove toxins from the blood, and they have a place in the treatment scheme, but due to the complex and multifunctional nature of the organ, some type of cell-based therapy is considered a more complete solution. 

This chapter will review the current state of the art in this arena. We first discuss the current methods for treating liver failure, including cell transplant techniques. The primary physical characteristics of successful implantable and extracorporeal devices will be described. We will then cover the work of Matsushita et al. that meets most of the requirements for a successful device along with improvements that will result from the use of hydrophilic-grafted polyurethanes. 

Liver cells were successfully transplanted for the first time in experiments on rats (A.X Matas et af, 1976 C.G. Groth et af, 1977). The requirements for transplantation include absolute care in the... 

Among the experimentally tested transplantation sites are the spleen, kidneys, lungs, pancreas, peritoneum, greater omentum and fatty tissue. Up to now, the spleen has proved to be the most suitable. The transplantation of foetal liver cells into the spleen may even culminate in a liver lobule-like formation with bile ducts and veins — however, the functional results have (so far) been no better than with normal hepatocytes. 

Indications for the transplantation of hepatocytes predominantly involve those liver diseases in which functional failures occur in the liver cells (not in the bile ducts). Permanent transplantation would be indicated, for example, in order to eliminate congenital metabolic disorders of the liver cells. In this case, hepatocytes from the patient could be used, with subsequent elimination of the defect by gene technology, as well as hepatocytes from healthy donors. A few years ago, a therapeutic effect lasting for over one year was achieved for the first time in a girl suffering from the Crigler-Najjar syndrome (I. X Fox et af, 1998). Human hepatocytes are most definitely more suitable than animal liver cells. The latter may well meet the requirements for a provisional substitute, but not for permanent transplantation. 

Kava extracts can, if overdosed (>60-120 mg kavapyr-ones/day) and/or taken over a longer period (>3 months), cause hepatotoxicity in the form of hepatic reactions and liver cell necrosis in rare cases, they may even cause cholestasis and acute liver failure (possibly leading to liver transplantation). Risk factors include the concomitant intake of medicaments and alcohol as well as a genetically based deficiency of cytochrome P450 2D6. (99, 116)... 

Occasionally, the liver is also involved slight increases in the transaminases and bilirubin, and possibly impaired excretory functions as well. Initially the hepatocytes reveal ultrastructural changes, and later slight steatosis and siderosis. The liver bioptate shows no signs of red fluorescence. In AIR, there is a high risk of cirrhosis and liver cell carcinoma developing. (266, 269, 294) In some patients suffering from such conditions, liver transplantation has proved successful. 

Kumar, K.S., Lefkowitch, J., Russo, M.W., Hesdorffer, C., Kinkhab-wala, M., Kapur, S., Emond, J.C., Brown, R.S. Successful sequential liver and stem cell transplantation for hepatic failure due to primary AL amyloidosis. Gastroenterology 2002 122 2026 - 2031... 

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