Erythropoietin expands a stromal cell population that can mediate renoprotection

• Published in: American Journal of Physiology - Renal Physiology Vol. 295; no. 4; pp. F1017 - F1022
• Main Authors: Bi, Baoyuan, Guo, Jiankan, Marlier, Arnaud, Lin, Shin Ru, Cantley, Lloyd G
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.10.2008
• Subjects: Acute Kidney Injury - chemically induced; Acute Kidney Injury - drug therapy; Acute Kidney Injury - pathology; Adipocytes - cytology; Adipocytes - drug effects; Animals; Antineoplastic Agents - toxicity; Apoptosis; Bone marrow; Cell culture; Cell Division - drug effects; Cell Survival - drug effects; Cells; Cells, Cultured; Cisplatin - toxicity; Drug Interactions; Erythropoietin - pharmacology; Female; Kidney Tubules - cytology; Kidney Tubules - drug effects; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - drug effects; Mice; Mice, Inbred C57BL; Receptors, Erythropoietin - metabolism; Rodents; Stromal Cells - cytology; Stromal Cells - drug effects; Studies
• ISSN: 1931-857X; 0363-6127; 1522-1466
• DOI: 10.1152/ajprenal.90218.2008

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.