Vasculotropic, paracrine actions of infused mesenchymal stem cells are important to the recovery from acute kidney injury.

作者: Florian Tögel , Kathleen Weiss , Ying Yang , Zhuma Hu , Ping Zhang

DOI: 10.1152/AJPRENAL.00339.2006

关键词:

摘要: Acute kidney injury (AKI) is a major clinical problem in which critical vascular, pathophysiological component recognized. We demonstrated previously that mesenchymal stem cells (MSC), unlike fibroblasts, are significantly renoprotective after ischemia-reperfusion and concluded this renoprotection mediated primarily by paracrine mechanisms. In study, we investigated whether MSC possess vasculoprotective activity may contribute, at least part, to an improved outcome AKI. MSC-conditioned medium contains VEGF, HGF, IGF-1 augments aortic endothelial cell (EC) growth survival, response not observed with fibroblast-conditioned medium. EC share vasculotropic gene expression profiles, as both form capillary tubes vitro on Matrigel alone or cooperation without fusion. undergo differentiation into endothelial-like phenotype culture develop vascular structures vivo. Infused were readily detected the early reflow but only rarely engrafted 1 wk post-AKI. attached renal microvascular circulation decreased apoptosis of adjacent cells. Infusion immediately severe AKI did improve blood flow, renovascular resistance, outer cortical flow. These data demonstrate unique vasculotropic, actions elicited play significant role AKI, further demonstrating therapy has promise novel intervention

参考文章(44)
Donald Orlic, Jan Kajstura, Stefano Chimenti, Igor Jakoniuk, Stacie M. Anderson, Baosheng Li, James Pickel, Ronald McKay, Bernardo Nadal-Ginard, David M. Bodine, Annarosa Leri, Piero Anversa, Bone marrow cells regenerate infarcted myocardium Nature. ,vol. 410, pp. 701- 705 ,(2001) , 10.1038/35070587
Timothy A. Sutton, Charles J. Fisher, Bruce A. Molitoris, Microvascular endothelial injury and dysfunction during ischemic acute renal failure Kidney International. ,vol. 62, pp. 1539- 1549 ,(2002) , 10.1046/J.1523-1755.2002.00631.X
D. Orlic, J. Kajstura, S. Chimenti, F. Limana, I. Jakoniuk, F. Quaini, B. Nadal-Ginard, D. M. Bodine, A. Leri, P. Anversa, Mobilized bone marrow cells repair the infarcted heart, improving function and survival Proceedings of the National Academy of Sciences of the United States of America. ,vol. 98, pp. 10344- 10349 ,(2001) , 10.1073/PNAS.181177898
Mayer Brezis, Seymour Rosen, Hypoxia of the Renal Medulla — Its Implications for Disease The New England Journal of Medicine. ,vol. 332, pp. 647- 655 ,(1995) , 10.1056/NEJM199503093321006
Florian Tögel, Jorge Isaac, Zhuma Hu, Kathy Weiss, Christof Westenfelder, Renal SDF-1 signals mobilization and homing of CXCR4-positive cells to the kidney after ischemic injury. Kidney International. ,vol. 67, pp. 1772- 1784 ,(2005) , 10.1111/J.1523-1755.2005.00275.X
Borhane Annabi, Ying-Ta Lee, Sandra Turcotte, Emmanuelle Naud, Richard R. Desrosiers, Martin Champagne, Nicoletta Eliopoulos, Jacques Galipeau, Richard Béliveau, Hypoxia promotes murine bone-marrow-derived stromal cell migration and tube formation. Stem Cells. ,vol. 21, pp. 337- 347 ,(2003) , 10.1634/STEMCELLS.21-3-337
Andrew E Wurmser, Fred H Gage, None, Cell fusion causes confusion Nature. ,vol. 416, pp. 485- 487 ,(2002) , 10.1038/416485A
William C. Kisseberth, Nicholas T. Brettingen, Jan K. Lohse, Eric P. Sandgren, Ubiquitous expression of marker transgenes in mice and rats. Developmental Biology. ,vol. 214, pp. 128- 138 ,(1999) , 10.1006/DBIO.1999.9417
Sergey V. Brodsky, Tokunori Yamamoto, Tetsuhiro Tada, Byungsoo Kim, Jun Chen, Fumihiko Kajiya, Michael S. Goligorsky, Endothelial dysfunction in ischemic acute renal failure: rescue by transplanted endothelial cells American Journal of Physiology-renal Physiology. ,vol. 282, ,(2002) , 10.1152/AJPRENAL.00329.2001
Yao Liang Tang, Qiang Zhao, Xinyu Qin, Leping Shen, Leilei Cheng, Junbo Ge, M. Ian Phillips, Paracrine action enhances the effects of autologous mesenchymal stem cell transplantation on vascular regeneration in rat model of myocardial infarction. The Annals of Thoracic Surgery. ,vol. 80, pp. 229- 237 ,(2005) , 10.1016/J.ATHORACSUR.2005.02.072