Towards Cell Therapy as a Replacement for Liver Transplant

The liver is the most regenerative of mammalian organs, so liver transplantation is the natural first candidate for replacement by some form of cell therapy, delivering cells that will regrow lost and damaged tissue. The details are important in these types of treatment, as seemingly small differences in the methodology of creating and transplanting cells leads to a wide variation in outcomes. A great deal of effort is devoted to finding exactly the right methodology for each tissue type in order to coax cells into carrying out regeneration, and here researchers demonstrate progress for liver tissue in rats:

Liver transplantation is currently the only established treatment for patients with end stage liver failure. However, this treatment is limited by the shortage of donors and the conditional integrity and suitability of the available organs. Transplanting donor hepatocytes (liver cells) into the liver as an alternative to liver transplantation also has drawbacks as the rate of survival of primary hepatocytes is limited and often severe complications can result from the transplantation procedure.

In an effort to find potential therapeutic alternatives to whole liver transplantation and improve the outcomes of hepatocyte transplantation, this study tested the therapeutic efficacy and feasibility of transplanting multi-layered sheets of hepatocytes and fibroblasts (connective tissue cells) into the subcutaneous cavity of laboratory rats modeled with end stage liver failure. The results of the study demonstrated that the cells in the multi-layered hepatocyte sheets survived better than cells transplanted by traditional methods and that the cells proliferated, maintaining liver function in the test animals for at least two months.

The researchers called the fibroblasts "feeder cells" that helped preserve the "high viability and functionality" of the hepatocytes in both in vitro and in vivo studies. The researchers also noted that in other methods of hepatocyte transplantation such as intrasplenic (through the spleen) or intraportal, only a small number of hepatocytes can be transplanted at one time, and many die. By contrast, the transplanted cell sheets showed "dramatically higher albumin expression levels" in vivo one month after transplantation into the subcutaneous cavity.

"Hypoxia is a major cause of poor hepatocyte survival. Therefore, immediately after transplantation, all transplanted cells are supplied with oxygen only from surface diffusion because of the lack of capillary vessels when other methods of transplantation are used." However, in the current study it was observed that merely one week after transplantation, the hepatocyte sheets were permeated with multiple capillary vessels. That the hepatocytes were close to blood vessels confirmed that vascularization is crucial for their survival and function.

Link: http://www.eurekalert.org/pub_releases/2015-08/ctco-ctp082615.php

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