Erythropoietin expands a stromal cell population that can mediate renoprotection.
Recent studies have demonstrated that erythropoietin (EPO) receptors are expressed on tubular epithelial cells and that EPO can protect tubular cells from injury in vitro and in vivo. Separate studies have demonstrated that marrow stromal cells (MSCs) exert a renoprotective effect in ischemia-reperfusion and cisplatin tubular injury via the secretion of factors that reduce apoptosis and increase proliferation of tubular epithelial cells. In the present study we demonstrate that MSCs express EPO receptors and that EPO can protect MSCs from serum deprivation-induced cell death and can stimulate MSC proliferation in vitro. The administration of EPO to mice resulted in the expansion of CD45-Flk1-CD105+ MSCs in the bone marrow and in the spleen and mobilized these cells as well as CD45-Flk1+ endothelial progenitor cells into the peripheral circulation. Consistent with previous reports, the administration of EPO diminished the decline in renal function associated with cisplatin administration. This effect was partially reproduced by intraperitoneal injection of cultured EPO-mobilized cells in cisplatin-treated mice. Thus the in vivo expansion and/or activation of these cells may contribute to the renoprotective effects of EPO to protect tubular cells from toxic injury.
Bi
Baoyuan
B
Yale University School of Medicine, 333 Cedar St., PO Box 208029, New Haven, CT 06510, USA.
Guo
Jiankan
J
Marlier
Arnaud
A
Lin
Shin Ru
SR
Cantley
Lloyd G
LG
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002945:Cisplatin / Q000633:toxicity; D004347:Drug Interactions; D004921:Erythropoietin / Q000494:pharmacology*; D005260:Female; D007684:Kidney Tubules / Q000166:cytology* / Q000187:drug effects; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D017467:Receptors, Erythropoietin / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology* / Q000187:drug effects*
D000970:Antineoplastic Agents; D017467:Receptors, Erythropoietin; D004921:Erythropoietin; D002945:Cisplatin