Paracrine effects of mesenchymal stem cells in cisplatin-induced renal injury require heme oxygenase-1

• Published in: American journal of physiology. Renal physiology Vol. 300; no. 1; p. F254
• Main Authors: Zarjou, Abolfazl, Kim, Junghyun, Traylor, Amie M, Sanders, Paul W, Balla, József, Agarwal, Anupam, Curtis, Lisa M
• Format: Journal Article
• Language: English
• Published: United States 01-01-2011
• Subjects: Acute Kidney Injury - chemically induced; Acute Kidney Injury - physiopathology; Acute Kidney Injury - prevention & control; Animals; Chemokine CXCL12; Cisplatin - toxicity; Culture Media, Conditioned - pharmacology; Heme Oxygenase-1 - deficiency; Heme Oxygenase-1 - physiology; Hepatocyte Growth Factor - secretion; Hypoxia - physiopathology; Male; Mesenchymal Stromal Cells - physiology; Mice; Multipotent Stem Cells; Neovascularization, Physiologic - physiology; Paracrine Communication - physiology; Vascular Endothelial Growth Factor A - secretion
• ISSN: 1522-1466
• DOI: 10.1152/ajprenal.00594.2010

Multipotent mesenchymal stem cells (MSC) have become a popular and promising therapeutic approach in many clinical conditions. MSC are beneficial in animal models of acute kidney injury (AKI), by mediating differentiation-independent paracrine properties, and have prompted ongoing clinical trials to evaluate the safety and efficacy of MSC. Heme oxygenase-1 (HO-1) is induced in response to stress including AKI and has important anti-apoptotic, anti-inflammatory, and proangiogenic properties in these settings. We therefore examined whether HO-1 plays a role in the beneficial effects of MSC in AKI. We isolated MSC from bone marrow of age-matched HO-1+/+ and HO-1-/- mice. Our studies indicate that while differentiation of MSC into osteo- and adipocytic lineages did not differ between cells isolated from HO-1+/+ and HO-1-/- mice, MSC from HO-1-/- mice had significantly lower angiogenic potential. Moreover, HO-1-/- MSC demonstrated reduced expression and secretion of several important growth and proangiogenic factors (stromal cell-derived factor-1, vascular endothelial growth factor-A, and hepatocyte growth factor) compared with MSC derived from HO-1+/+ mice. In addition, conditioned medium of HO-1+/+ MSC rescued functional and morphological changes associated with cisplatin-induced AKI, while the HO-1-/--conditioned medium was ineffectual. Our studies indicate that HO-1 plays an important role in MSC-mediated protection. The results expand understanding of the renoprotective effects of MSC and may provide novel strategies to better utilize MSC in various disease models.