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

Abstract

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

Multipotent mesenchymal stromal cells for autoimmune diseases: teaching new dogs old tricks

“…59 In another study it was shown that the renoprotective effect of MSCs was mediated by the mitogenic and pro-survival insulin growth factor-1 (IGF-1) produced by the MSCs. 60 Recently, a vasculotropic effect of infused MSC in the kidney was shown, 61 which may be relevant to SSc.…”

Vascular Endoluminal Delivery of Mesenchymal Stem Cells Using Acoustic Radiation Force

“…19 To this point, MSCs secrete vascular endothelial growth factor, insulin-like growth factor, and hematopoietic growth factor, 20 stimulate endogenous angiogenesis, and have a positive effect on the endothelium. 21 Further, unlike EPCs, MSCs have already been clinically used in an allogeneic fashion, primarily for their indirect regenerative and anti-inflammatory properties, 22,23 and thus can be readily available to clinicians.…”

Adult stem cells: potential implications for perioperative medicine

“…12 Mesenchymal stromal cells have also proven useful in preclinical acute kidney injury where they displayed potent anti-apoptotic and cytoprotective effects. 13 Interestingly, in preclinical sepsis models, MSCs not only improved survival and organ function but also showed potent antibacterial effects. 14 Given these organ protective effects as well as the ability to clear pathogens, it is clear that MSCs could have potential benefits for many patients in the perioperative period.…”

“…12 Les cellules stromales mésenchymateuses se sont également avérées utiles dans le traitement des lésions rénales aiguës précliniques, où elles ont démontré d'importants effets anti-apoptotiques et cytoprotecteurs. 13 Il est intéressant de mentionner que, dans des modèles précliniques de sepsis, les CSM ont non seulement amélioré la survie et la fonction des organes, mais ont également démontré de puissants effets antibactériens. 14 É tant donné ces effets protecteurs sur les organes ainsi que leur capacité à éliminer les pathogènes, il est clair que les CSM pourraient avoir des bienfaits potentiels pour de nombreux patients en période périopératoire.…”