Opening the Window


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Prof. Yari Reiser and his team. Transplant cells


Diabetics, particularly those afflicted with Type 1 (juvenile) diabetes, face a lifetime of daily injections to replace the insulin their bodies fail to produce, as well as a host of risks, including blindness, amputation, kidney failure and heart disease. New treatments for diabetes in recent years include the transplantation of human pancreatic tissue in which insulin is produced. Unfortunately, this sort of transplant remains an option for only a few, as there are not nearly enough donor organs available. 
Many animals produce insulin, and the insulin-producing cells of pigs, in particular, are very similar to those of humans. If this tissue could be transplanted into humans, millions of diabetics might benefit. The only catch is that our immune systems are quite vigilant in rejecting any foreign tissue, no matter how similar. Pancreatic tissue from animals that has been experimentally transplanted into non-human primates has, until now, evoked a fierce immune response. 
Embryonic tissue, however, might be more easily adapted to the human body. New research by Prof. Yair Reisner of the Weizmann Institute's Immunology Department has brought the possibility of transplants from pig embryos one step closer. In an article that appeared in PLoS Medicine, Reisner and his team demonstrated how proper timing may be the key.  
In previous work, Reisner and his team had shown that each embryonic organ has its own "time window" during which the chances for successful transplantation are optimal. Prior to this window, the early tissue's cells, which are still largely undifferentiated, can give rise to tumors. Past the window, however, they may be too well developed: They already carry too many markers that identify them as foreign, causing the body to reject them. By transplanting tissue from pig embryos into mice lacking proper immune systems, the researchers determined that the best time frame for pancreatic tissue was about a third of the way through gestation (from 42 to 56 days).
In the new study, Reisner's team wanted to see how such transplanted tissue might function in the body. They first implanted embryonic tissue from pig pancreases into special mice that had human immune cells circulating in their systems - creating a sort of surrogate human immune system. From this experiment they learned that when tissue taken at 42 days (within the time frame they had previously determined) was used, the immune response was markedly reduced.  
Next, the team tried the experiment on mice with fully functioning mouse immune systems, but they destroyed the insulin-producing cells in the mice's pancreases before proceeding with the transplant. With the aid of relatively mild immune suppression protocols, the implanted tissue was fully functional over time, producing insulin and maintaining the mice's blood sugar at normal levels.
According to Reisner, the next logical step would be preclinical trials on non-human primate models. Although the road to pig embryo-human transplants is still a long and uncertain one, if further studies bear out the team's findings, regular insulin injections could one day become a thing of the past for many diabetics.    

Prof. Yair Reisner's research is supported by the J & R Center for Scientific Research; the Belle S. and Irving E. Meller Center for the Biology of Aging; the Gabrielle Rich Center for Transplantation Biology Research; the Abisch Frenkel Foundation for the Promotion of Life Sciences; the Loreen Arbus Foundation; the Crown Endowment Fund for Immunological Research; the Mario Negri Institute for Pharmacological Research - Weizmann Institute of Science Exchange Program; the Charles and David Wolfson Charitable Trust; Renee Companez, Australia; Mr. and Mrs. Irwin Goldberg, Las Vegas, NV; and Mr. and Mrs. Barry Reznik, Brooklyn, NY. Prof. Reisner is the incumbent of the Henry H. Drake Professorial Chair in Immunology.