Amelioration of Acute Renal Failure by Stem Cell Therapya€”Paracrine Secretion Versus Transdifferentiation into Resident Cells Administered Mesenchymal Stem Cells Protect against Ischemic Acute Renal Failure through Differentiation-Independent Mechanisms. Am J Physiol Renal Physiol E-pub February 15, 2005

摘要

Although the kidney has been suspected, though not definitively proven, to contain organ-specific pluripotent stem cells, their role in regeneration after renal injury is uncertain (1a€“3). Recently, however, several investigators found evidence for a renoprotective role of nona€“organ-specific stem cells in acute renal failure. Arriero et al. (4) reported dramatic protection of the kidney against ischemia/ reperfusion injury after injection of in vitro expanded skeletal muscle-derived stem cells, differentiated along the endothelial lineage (but not after injection of nondifferentiated stem cells). The renal function after ischemia was improved and engraftment of the transplanted cells into the renal microvasculature was documented. Morigi et al. (5) studied the cisplatin model of acute renal failure: Injection of mesenchymal stem cells (MSC) of bone marrow origin, but not injection of hematopoietic cells, protected syngeneic female mice against severe tubular injury and renal functional impairment. Furthermore, engraftment of MSC into the vigorously proliferating tubular epithelial cell layer was documented by demonstration of Y-chromosomea€“containing cells. In the same model, Iwasaki et al. (6) showed that pretreatment with G-CSF and M-CSF with the rationale to mobilize bone marrowa€“derived stem cells prevented renal tubular injury and accelerated recovery of renal function. Furthermore, cells expressing markers of bone marrowa€“derived cells were documented in the tubular epithelial cell layer. Finally, in acute renal failure after ischemia/reperfusion injury, Lin et al. (7) showed that hematopoietic stem cells contributed to the regeneration of renal tubular epithelial cells. In the kidneys of nontransgenic female recipients that had been subjected to unilateral ischemia, the authors showed that still after 4 wk ?2-galactosidasea€“expressing Y chromosomea€“positive cells from transgenic male donors were detected. The authors suggested that their findings are accounted for by a€?transdifferentiation,a€? i.e., phenotypic conversion of pluripotent somatic stem cells of one tissue type to another tissue type as had previously been postulated by other authors (8,9). The authors could not exclude, however, cell hybridization, i.e., the possibility that bone marrowa€“derived cells adopted the phenotype of other cell lineages by fusion (10,11).