Xenobiotic Kidney Organogenesis from Human Mesenchymal Stem Cells Using a Growing Rodent Embryo

摘要: Given the limits of allogenic organ transplantation, an ultimate therapeutic solution is to establish a self-organ from autologous stem cells and transplant them as syngrafts back into donor patients. It was reported previously that human mesenchymal (hMSC) are cultivated in growing rodent embryos can differentiate within spatially temporally appropriate developmental milieu, facilitating first step nephrogenesis. As another toward clinical application, system modified for progression complete functional organogenesis. Rat (E11.5) were isolated uteri, bone marrow-derived hMSC, which transfected adenovirally with glial cell line-derived neurotrophic factor retrovirally LacZ, implanted nephrogenic site. Forty-eight hours later, ureteric buds elongated initial branching completed. The metanephroi dissected out, developed further using vitro culture 24 h, transplanted omentum uninephrectomized rat, grown 2 wk. They enlarged exhibited normal kidney structure ultrastructure. hMSC-derived LacZ-positive identified throughout regenerated morphologically identical resident renal cells. Transplantation developing LacZ transgenic rat revealed neo-kidney vasculature originated host circulation. Finally, fluid collected expanded ureters, urea nitrogen creatinine measured. Levels much higher these fluids compared sera (840.3 +/- 184.6 versus 30.4 10.8 10.1 3.1 0.3 0.2 mg, respectively), suggesting may produce urine. Taken together, findings suggest hMSC mature potential replace lost function.