Kidney tissue reconstruction by fetal kidney cell transplantation: Effect of gestation stage of fetal kidney cells

Abstract

Dialysis and kidney transplantation, current therapies for kidney failure, have limitations such as severe complications, donor shortage, and immune-related problems. The development of an alternative treatment for kidney failure is demanded. The present study shows that the transplantation of fetal kidney cells reconstitutes functional kidney tissue, and that the gestation stage of kidney cells influences the kidney reconstitution. Fetal kidney cells were isolated from metanephroi of rat fetuses at various gestation stages and transplanted into the omentum or kidney of immunodeficient mice. Immunophenotype analysis of fetal kidney cells showed apparent expression of stem cell markers. Three weeks after transplantation, histological analyses of retrieved grafts revealed the formation of kidney structures, including fluorescently labeled transplanted cells, suggesting the potential of fetal kidney cells to reconstitute kidney tissues. The grafts retrieved from omentum contained cystic fluids with concentrated solutes. However, transplanted early fetal kidney cells had also differentiated into nonrenal tissues such as bone and cartilage. In addition, transplantation of fetal kidney cells from a later gestation stage resulted in poor kidney structure formation. Kidney-specific genes were strongly expressed in the earlier cell transplants. The cells at an earlier gestation stage had higher colony forming ability than the cells at a later stage. This study demonstrates the reconstitution of kidney tissue by transplanting fetal kidney cells and the presence of an optimal time window in which fetal kidney cells regenerate kidney tissues.