Abstract
Lack of donor availability limits the number of human donor organs. The need for host immunosuppression complicates transplantation procedures. Ultrastructurally precise kidneys differentiate in situ following xenotransplantation in mesentery of embryonic pig renal primordia. The developing organ attracts its blood supply from the host, obviating humoral rejection. Engraftment of pig renal primordia transplanted directly into rats requires host immune suppression. However, insulin-producing cells originating from embryonic pig pancreas obtained very early following initiation of organogenesis [embryonic day 28 (E28)] engraft long term in nonimmune-suppressed diabetic rats or rhesus macaques. Engraftment of morphologically similar cells originating from adult porcine islets of Langerhans (islets) occurs in rats previously transplanted with E28 pig pancreatic primordia. Here, we review recent findings germane to xenotransplantation of pig renal or pancreatic primordia as a novel organ replacement strategy.
Highlights
Transplantation of embryonic renal or pancreatic primordia to replace the function of diseased organs offers theoretical advantages relative to transplantation of either pluripotent ES cells or of fully differentiated organs (Reviewed in [1, 2]). (1) Unlike embryonic stem (ES) cells, organ primordia differentiate along defined organ-committed lines
There is no requirement to steer differentiation and no risk of teratoma formation; (2) the growth potential of cells within embryonic organs is enhanced relative to those in terminally differentiated organs; (3) the cellular immune response to transplanted primordia obtained early during embryogenesis is attenuated relative to that directed against adult organs; (4) early organ primordia are avascular
We have shown that glucose tolerance can be normalized in streptozotocin- (STZ-) diabetic LEW [7, 8, 12] rats or ZDF diabetic rats [10] within 4 weeks following transplantation in mesentery of pig pancreatic primordia obtained very early during embryogenesis (on embryonic day 28 (E28)—just after the organ differentiates and prior to the time dorsal and ventral anlagen fuse) without host immune suppression
Summary
Transplantation of embryonic renal or pancreatic primordia to replace the function of diseased organs offers theoretical advantages relative to transplantation of either pluripotent ES cells or of fully differentiated (adult) organs (Reviewed in [1, 2]). (1) Unlike embryonic stem (ES) cells, organ primordia differentiate along defined organ-committed lines. Transplantation of embryonic renal or pancreatic primordia to replace the function of diseased organs offers theoretical advantages relative to transplantation of either pluripotent ES cells or of fully differentiated (adult) organs (Reviewed in [1, 2]). (1) Unlike embryonic stem (ES) cells, organ primordia differentiate along defined organ-committed lines. The ability of cellular primordia to attract a host vasculature renders them less susceptible to humoral rejection than are adult organs with donor blood vessels transplanted across a discordant xenogeneic barrier; (5) organ primordia differentiate selectively. In the case of embryonic pancreas, exocrine pancreatic tissue does not differentiate following transplantation, obviating complications that can result from exocrine components such as the enzymatic autodigestion of host tissues. While the transplantation of human embryonic organs in human hosts has been contemplated [3,4,5], we [6,7,8,9,10,11,12,13] and others [4, 5, 14,15,16,17] have focused on the use of embryonic organs from the pig, a physiologically suitable donor for human pancreas or kidney replacement [18, 19]
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