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Thread: Human Kidneys Created In Mice: Transplanted Tissue Could Offer A Solution To Kidney Donor Shortage

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    Senior Member Max's Avatar
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    Human Kidneys Created In Mice: Transplanted Tissue Could Offer A Solution To Kidney Donor Shortage

    Human Kidneys Created In Mice: Transplanted Tissue Could Offer A Solution To Kidney Donor Shortage
    Rehovot, Israel (December 22, 2002) -- Instead of searching for a kidney donor, a new study suggests, one might be able to grow a new kidney. A team headed by Prof. Yair Reisner of the Weizmann Institute of Science has induced human stem cell tissue to grow into functional kidneys, and have accomplished the same with porcine stem cell tissue. Published in Nature Medicine, the method could lead to a promising solution to the severe shortage of kidney donors.
    The findings suggest that human or porcine fetal tissue might take on the shape and function of a healthy kidney if transplanted into humans as well. Pig tissue, as opposed to pig organs, is not expected to cause hyperacute rejection (common in cross-species transplants), as has been demonstrated by recent transplants of insulin-producing cell clusters taken from porcine fetal tissue that did not induce such rejection. The scientists hope that porcine stem cells might thus provide a ubiquitous source for those in need of a kidney.

    According to the U.S. National Kidney Foundation and the United Network for Organ Sharing, more than 50,000 people in the United States alone are on the waiting list for kidney transplants and more than 2,000 died this year waiting for a match. The wait can last years. And after a kidney is transplanted patients run the risk of transplant rejection.

    Reisner and Ph.D. student Benny Dekel of the Weizmann Institute's Immunology Department, with Prof. Justen Passwell, the head of the pediatric department at the Sheba Medical Center, transplanted human and porcine "kidney precursor cells" (stem cells that are destined to become kidney cells) into mice. Both human and porcine tissues grew into perfect kidneys, the size of the mice's kidneys. The miniature human and pig kidneys were functional, producing urine. In addition, blood supply within the kidney was provided by host blood vessels as opposed to donor blood vessels, greatly lowering the risk of rejection.

    The scientists pinpointed the ideal time during embryonic development in which the stem cells have the best chance to form well-functioning kidneys with minimal risk for immune rejection. Their findings suggest that 7-8 week (human) and 4 week (porcine) tissue offers an optimal window of opportunity for transplantation. If taken at earlier time points the tissues will develop disorganized tissue that would include non-kidney structures such as bone, cartilage, and muscle. If taken at later time points the risk for immune rejection is substantial.

    Within this optimal time range the tissue doesn't contain certain cells that the body recognizes as foreign (antigen-presenting cells), the scientists found. These cells, which originate in the blood system, reach a developing kidney only after ten weeks.

    After growing the human and porcine kidney tissue in mice, the scientists checked how human lymphocytes (fighter cells in the immune system) might react to it. They injected human lymphocytes into immunodeficient mice (that have no immune system and thus do not interfere with the immune response). The findings were encouraging: as long as the kidney precursors were transplanted within the right time range, the lymphocytes did not attack the new pig or human kidneys - despite the fact that lymphocytes and kidney precursors originated from different donors. Immune rejection was also tested in normal mice and was shown to be reduced compared to that induced by precursors from later time points.

    The procedure is now in the pre-clinical study stage. If all goes well, a treatment may ensue within a few years.


    ###


    Prof. Reisner is the incumbent of the Henry H. Drake Professorial Chair in Immunology. His research is supported by Richard M. Beleson, San Francisco, CA, Renee Companez, Australia, Concern Foundation, Ligue Nationale Francaise Contre Le Cancer, M.D. Moross Institute for Cancer Research, Gabrielle Rich Leukemia Research Foundation, Rowland Schaefer, Pembroke Pines, FL, Union Bank of Switzerland-Optimus Foundation.

    The Weizmann Institute of Science, in Rehovot, Israel, is one of the world's foremost centers of scientific research and graduate study. Its 2,500 scientists, students, technicians, and engineers pursue basic research in the quest for knowledge and the enhancement of humanity. New ways of fighting disease and hunger, protecting the environment, and harnessing alternative sources of energy are high priorities at Weizmann.



    --------------------------------------------------------------------------------

    Note: This story has been adapted from a news release issued for journalists and other members of the public. If you wish to quote any part of this story, please credit Weizmann Institute as the original source. You may also wish to include the following link in any citation:


    http://www.sciencedaily.com/releases...1223083434.htm

    [This message was edited by Max on Dec 23, 2002 at 11:54 AM.]

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    Senior Member Max's Avatar
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    Working kidney grown in mouse

    Working kidney grown in mouse


    01:00 23 December 02
    James Randerson


    Complete working kidneys have been grown in mice using stem cells derived from human and pig fetuses. If the feat can be repeated in humans, it will allow doctors to replace damaged organs without the need for a donor.

    The Israeli team, who used three-month-old mice as recipients for the growing kidneys, were able to avoid immune rejection by using embryonic stem cells. The developing kidney takes time to acquire 'antigen presenting cells' which are recognised by the host immune system as foreign.

    Embryonic stem cells are also able to adapt to their host, reducing the chance that they will be rejected later in development, says Camillo Ricordi, University of Miami, who works on transplanting islet cells into the pancreas to cure type I diabetes.

    "Our data pinpoint a window ... that may be optimal for transplantation in humans," say the researchers in their paper in Nature Medicine. If the cells are too young, they do not develop into all the necessary cell types. But if taken too late, the developing kidney will be rejected.

    The kidneys functioned well enough to produce dilute urine. But the organs did not connect up with the host's excretory system. Instead, the researchers, led by Yair Reisner at the Weizmann Institute of Science in Rehovot, Israel, connected a catheter directly into the developing organ. If the technique were used on patients, surgery would be required to connect up the developing kidney.


    Safety questions


    Reisner's team hopes that if the technique can be applied to humans it will mean an end to the years of waiting that patients often have to undergo for a donor. Over 50,000 people are on the waiting list for a kidney transplant in the US and more than 2000 people die annually waiting for a match.

    However, growing a kidney from pig cells transplanted into a human body will raise safety questions. There are fears that such xenotransplantation could allow porcine endogenous retroviruses (PERVs), which are present in the pig genome, to jump to a human host.

    "That is always a concern," says Ricordi. "But more and more data support the fact that it is not a possibility." Hundreds of patients have been given pig islet cells, but none have shown signs of the virus.

    Using human embryonic stem cells would avoid the risk of PERVs but involves the destruction of human embryos, which is ethically unacceptable to some.

    Journal reference: Nature Medicine (DOI:10.1038/nm812)


    01:00 23 December 02

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  3. #3
    Author Topic: テつ* Human Kidneys Created In Mice: Transplanted Tissue Could Offer A Solution To Kidney Donor Shortage

    DA

    Member posted Dec 23, 2002 04:37 PM テつ*
    ------------------------------------------------------------------------
    http://www.sciencedaily.com/releases...1223083434.htm


    Rehovot, Israel (December 22, 2002) -- Instead of searching for a kidney donor, a new study suggests, one might be able to grow a new kidney. A team headed by Prof. Yair Reisner of the Weizmann Institute of Science has induced human stem cell tissue to grow into functional kidneys, and have accomplished the same with porcine stem cell tissue. Published in Nature Medicine, the method could lead to a promising solution to the severe shortage of kidney donors.
    The findings suggest that human or porcine fetal tissue might take on the shape and function of a healthy kidney if transplanted into humans as well. Pig tissue, as opposed to pig organs, is not expected to cause hyperacute rejection (common in cross-species transplants), as has been demonstrated by recent transplants of insulin-producing cell clusters taken from porcine fetal tissue that did not induce such rejection. The scientists hope that porcine stem cells might thus provide a ubiquitous source for those in need of a kidney.

    According to the U.S. National Kidney Foundation and the United Network for Organ Sharing, more than 50,000 people in the United States alone are on the waiting list for kidney transplants and more than 2,000 died this year waiting for a match. The wait can last years. And after a kidney is transplanted patients run the risk of transplant rejection.

    Reisner and Ph.D. student Benny Dekel of the Weizmann Institute's Immunology Department, with Prof. Justen Passwell, the head of the pediatric department at the Sheba Medical Center, transplanted human and porcine "kidney precursor cells" (stem cells that are destined to become kidney cells) into mice. Both human and porcine tissues grew into perfect kidneys, the size of the mice's kidneys. The miniature human and pig kidneys were functional, producing urine. In addition, blood supply within the kidney was provided by host blood vessels as opposed to donor blood vessels, greatly lowering the risk of rejection.

    The scientists pinpointed the ideal time during embryonic development in which the stem cells have the best chance to form well-functioning kidneys with minimal risk for immune rejection. Their findings suggest that 7-8 week (human) and 4 week (porcine) tissue offers an optimal window of opportunity for transplantation. If taken at earlier time points the tissues will develop disorganized tissue that would include non-kidney structures such as bone, cartilage, and muscle. If taken at later time points the risk for immune rejection is substantial.

    Within this optimal time range the tissue doesn't contain certain cells that the body recognizes as foreign (antigen-presenting cells), the scientists found. These cells, which originate in the blood system, reach a developing kidney only after ten weeks.

    After growing the human and porcine kidney tissue in mice, the scientists checked how human lymphocytes (fighter cells in the immune system) might react to it. They injected human lymphocytes into immunodeficient mice (that have no immune system and thus do not interfere with the immune response). The findings were encouraging: as long as the kidney precursors were transplanted within the right time range, the lymphocytes did not attack the new pig or human kidneys - despite the fact that lymphocytes and kidney precursors originated from different donors. Immune rejection was also tested in normal mice and was shown to be reduced compared to that induced by precursors from later time points.

    The procedure is now in the pre-clinical study stage. If all goes well, a treatment may ensue within a few years.
    ------------------------------------------------------------------------
    Posts: 1712テつ*|テつ*From: beaumont tx usaテつ*|テつ*Registered: Jul 24, 2001

  4. #4
    Senior Member Jeff's Avatar
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    This is incredibly awesome news

    Many SCI have damaged kidneys. And think of the money saved by not requiring ongoing dialysis for those with chronic kidney failure.

    The new world of medicine is finally getting here!

    ~See you at the SCIWire-used-to-be-paralyzed Reunion ~

  5. #5
    Here is the reprint
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