Bone marrow stem cells contribute to repair of the ischemically injured renal tubule

Abstract

The paradigm for recovery of the renal tubule from acute tubular necrosis is that surviving cells from the areas bordering the injury must migrate into the regions of tubular denudation and proliferate to re-establish the normal tubular epithelium. However, therapies aimed at stimulating these events have failed to alter the course of acute renal failure in human trials. In the present study, we demonstrate that Lin -Sca-1 + cells from the adult mouse bone marrow are mobilized into the circulation by transient renal ischemia and home specifically to injured regions of the renal tubule. There they differentiate into renal tubular epithelial cells and appear to constitute the majority of the cells present in the previously necrotic tubules. Loss of stem cells following bone marrow ablation results in a greater rise in blood urea nitrogen after renal ischemia, while stem cell infusion after bone marrow ablation reverses this effect. Thus, therapies aimed at enhancing the mobilization, propagation, and/or delivery of bone marrow stem cells to the kidney hold potential as entirely new approaches for the treatment of acute tubular necrosis.This article was published online in advance of the print edition. The date of publication is available from the JCI website, http://www.jci.org.

Bone marrow-derived pluripotent very small embryonic-like stem cells (VSELs) are mobilized after acute myocardial infarction

“…In this regard, exogenous cytokine-induced mobilization of BMCs has been shown to be beneficial after stroke as well as MI [6,28]. Moreover, the identification of BMC-derived cells in various injured tissues, including brain, liver, kidney, lung, and heart, indicates that tissue injury can induce mobilization of BMCs from the marrow into the PB [1][2][3][4][5]7,8]. However, the mobilization of pluripotent stem cells after acute MI has never been reported.…”

“…BM-derived cells (BMCs) have been shown to participate in tissue repair following injury to several organs, including the brain, liver, lung, kidney [1][2][3][4][5] as well as the heart [6][7][8][9][10][11]. Cardiomyocytes derived from BMCs have been noted in the heart after myocardial infarction (MI) [6,7,10].…”

The pleiotropic effects of the SDF-1–CXCR4 axis in organogenesis, regeneration and tumorigenesis

“…97,98 This mechanism had been proposed for heart infarct, 39,99 stroke, 100,101 liver damage, 102 kidney damage, 43,103 pancreatic damage, 104 skeletal muscle injury, 105 bone fractures 106 and lung damage. 107 Accordingly, during these various organ/tissue injury models, there were circulating cells identified in PB that express markers for endothelial-, mesenchymal-, cardiac-, skeletal muscle-, liver-, kidney, neural-and bone-NSC.…”

Bone marrow‐derived very small embryonic‐like stem cells: Their developmental origin and biological significance

“…Several investigators in the past few years have demonstrated that BM-derived cells can contribute to the regeneration of nonhematopoietic organs and tissues (Jackson et al, 2001;Orlic et al, 2001;Corbel et al, 2003;Kale et al, 2003). These observations were mainly explained by the hypothesis that HSC are "plastic" and, thus, could trans-dedifferentiate into stem cells committed for various organs and tissues (Mezey et al, 2000;Corti et al, 2002b).…”

“…HSC and other nonhematopoietic stem cells are actively chemoattracted by factors secreted by BM stroma cells and osteoblasts (e.g., stromal derived factor-1 [SDF-1] and hepatocyte growth factor [HGF]) and colonize marrow by the end of the second and the beginning of the third trimester of gestation (Kmiecik et al, 1992;Ma et al, 1998;Nagasawa, 2000;Taichman et al, 2001). Accumulating evidence suggests that these nonhematopoietic stem cells residing in the BM play some role in the homeostasis/turnover of peripheral tissues and if needed could be released/mobilized from the BM into circulation during tissue injury and stress, thus facilitating the regeneration of damaged organs (LaBarge and Blau, 2002;Kale et al, 2003;Kollet et al, 2003;Abbott et al, 2004;Kucia et al, 2004Kucia et al, , 2006cWojakowski et al, 2004;Long et al, 2005;Gomperts et al, 2006). It is also possible that, in steady state conditions, they shuttle at very low level between BM and stem cell niches in peripheral organs/tissues.…”