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    Interspecies Transplant Works - Without Immunosuppressive Drugs
    By News Staff | July 12th 2013 01:06 PM | 1 comment | Print | E-mail | Track Comments

    At some point it would be ideal for animal-to-human transplants of insulin-producing cells for people with type 1 diabetes, such as from pigs, but first there must be baby steps.

    Or in this case, mouse steps.

    Scientists have successfully transplanted islets, the cells that produce insulin, from a rat to a mouse. Using their new method of xenotransplantation, the islets survived without immunosuppressive drugs.

    For people with hard-to-control type 1 diabetes, a transplant of insulin-producing islets from a deceased donor is one important way to control their chronic disease, in which their bodies do not produce insulin. However, there is a severe shortage of islet cells from deceased donors. Many patients on waiting lists don't receive the transplant or suffer damage to their heart, nerves, eyes and kidneys while they wait.

    Using islets from another species would provide wider access to transplants for humans and solve the problem. But concerns about controlling rejection of transplants from a different species have made that approach seem insurmountable until now.

    In the new study, the scientists persuaded the immune systems of mice to recognize rat islets as their own and not reject them. Notably, the method did not require the long-term use of drugs to suppress the immune system, which have serious side effects. The islets lived and produced insulin in the mice for at least 300 days, which is as long as scientists followed the mice.  

    While the barrier from rats to mice is probably lower than from pigs to humans, the study showed interspecies islet transplants are possible and without immunosuppressive drugs.

    In the study, the rat splenocytes, a type of white blood cell located in the spleen, were removed and treated with a chemical that caused their deaths. Next, the dead splenocytes were injected into the mice. The cells entered the spleen and liver and were mopped up by scavenger cells. The scavengers processed the splenocytes and presented fragments of them on their cell surface, triggering a reaction that told the T cells to accept the subsequently transplanted rat islets and not attack them.

    But rejection was still a threat. A unique challenge of an interspecies transplant is controlling the B cells, immune cells that are major producers of antibodies. Initially, when the scientists transplanted the rat islets into the mice, the mouse immune system started producing antibodies against the rat cells causing rejection.

    To solve the problem,  Xunrong Luo, M.D., co-senior author and associate professor of nephrology at Northwestern,  realized they needed to kill off the B-cells at the same time she injected the donor islets into the mice. Thus, she gave the mice B-cell depleting antibodies -- already used in a clinical setting in human transplants. When the B-cells naturally returned after the transplant, they no longer attacked the rat islets.

    "With this method, 100 percent of the islets survived indefinitely," Luo said. "Now we're trying to figure out why the B-cells are different when they come back."

    "This is the first time that an interspecies transplant of islet cells has been achieved for an indefinite period of time without the use of immunosuppressive drugs," said study co-senior author and Northwestern Professor of Microbiology-Immunology Stephen Miller. "It's a big step forward." 


     Published in Diabetes.


    Comments

    Herne Webber
    This is a truly *horrible* idea for two reasons.

    1) Doing this extends the ethical consideration of the use of animals as disposable things.  I wish to extend the ethical consideration that animals have the right to their own self-determination, since we have the option to choose whether or not to harm them.  Why not choose letting them be?

    2) The reason probably more compelling to the average reader is the very probable occurrence of an interspecies viral infection/transfection.  This could be especially bad for species such as pigs, which share influenza receptors with both humans and birds.  Putting living pig cells into a human skips a step, only needing contact with both an infected bird and another person infected with ordinary flu.  Would the presence of pig cells make the blending and creation of a potentially deadly flu strain more likely?  Because it certainly would not make it *less* likely!  And that is just naming one possible scenario.  Imagine creating a new type of hepatitis (from at least three different viral clades), or HIV, because of foreign species' cells being at hand for generations of virus to attempt to enter them.  HIV already mutates within its host to expand its repertoire of cell lines it can infect, going from one type of immune cell in the mucosa into T-cells, and then into other immune cells, and eventually into neurons.  No, we need to NOT use other species' cells in the manner described in this article.