Human Kidneys Created in Mice


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Transplanted tissue could offer a solution to kidney donor shortage

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.
Top (arrow): Transplant of a human kidney originating from an 8-week old embryo, 8 weeks after transplantation. Bottom: Tissue sections of the kidney transplant at varying magnifications indicating differentiation into various cell structures.
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 top-ranking multidisciplinary research institutions. Noted for its wide-ranging exploration of the natural and exact sciences, the Institute is home to 2,500 scientists, students, technicians and supporting staff. Institute research efforts include the search for new ways of fighting disease and hunger, examining leading questions in mathematics and computer science, probing the physics of matter and the universe, creating novel materials and developing new strategies for protecting the environment.