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Scientists at the Weizmann Institute of Science have determined distinct gestational time windows for the growth of transplanted pig embryonic liver, pancreas and lung precursor tissue into functioning organs in mice. These findings – appearing this week in PNAS online Early Edition – could help enhance the chances for successful implementation of embryonic pig tissue in the treatment of a wide spectrum of human diseases.
The study, led by Prof. Yair Reisner of the Institute's Immunology Department, involved the extraction of embryos from sows at various stages of pregnancy and implantation of organ-committed cell tissue into immunodeficient mice. His novel approach did not involve the growth of any tissue in culture. The analysis of embryonic-tissue at various gestational ages revealed a unique pattern of growth and differentiation for each organ.
The potential of embryonic pig tissues as a new source for organ transplantation in humans has been advocated for more than two decades. Transplant too early, however, and the risk is undifferentiated embryonic tissue that can develop into undesirable and possibly malignant tissue, a type of tumor known as "teratoma." Transplant too late and the risk is that the tissues will have reached the stage where they have been marked with certain identifiers that trigger rejection by the new host.
The study demonstrated that maximal liver growth and function were achieved at the earliest teratoma-free gestational age (four weeks). The growth and functional potential of the pancreas occurred later (six weeks) and its optimal transplant age limit was defined by a decline in the insulin-secreting capacity beyond 10 weeks gestational age. Development of mature lung tissue containing essential respiratory system elements was observed at a relatively late gestational age. The sequence of transplanted organ development paralleled that of normal embryonic development in which the liver and pancreas precede the lungs.
“Disappointing results in past transplantation trials may be explained, at least in part, by these results,” says Reisner. Early studies that attempted to cure diabetic patients by implantation of pig embryonic pancreas, made use of late gestation tissue which is now shown to be inferior compared to the optimal six weeks gestational time.
In previous studies, Reisner's group demonstrated that transplanted human and pig kidney embryonic tissue could grow into miniature, functioning human or pig kidneys inside a mouse. His novel approach was a matter of timing: Gestational age proved to be the key to successful kidney growth from transplanted embryonic tissue.
Prof. Yair Reisner's chair is supported by the M.D. Moross Institute for Cancer Research, the Gabrielle Rich Center for Transplantation Biology Research (Head), the J & R Center for Scientific Research, the Belle S. & Irving E. Meller Center for the Biology of Aging, the Abisch Frenkel Foundation for the Promotion of Life Sciences, Richard M. Beleson, San Francisco, CA, Renee Companez, Australia, the Crown Endowment Fund for Immunological Research, Erica A. Drake, Scarsdale, NY, the Ligue Nationale Francaise Contre le Cancer, Mr. and Mrs. Barry Reznik, Brooklyn, NY, and the Union Bank of Switzerland-Optimus Foundation .
Prof. Reisner is the incumbent of the Henry H. Drake Professorial Chair in Immunology.
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.