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.

Intra Renal Arterial Injection of Autologous Mesenchymal Stem Cells in an Ovine Model in the Postischemic Kidney

“…Several publications showed engraftment and differentiation of grafted SC into renal structures associated with improvement in renal function [3,5,6,7,8,9]. However, other studies demonstrated beneficial effect in spite of low presence or even absence of SC engraftment [10,11,12].…”

“…Most published studies [7,8,9,10,12,13,14] have used valuable rodent models to investigate SC therapy in the kidney. However, in small animal models, autologous graft is difficult owing to the size of the animal and immunosuppressive treatments are necessary in order to avoid rejection and enable SC survival.…”

“…When chimera were used cells were not injected but were present at the time of the onset of the injury [7, 8,10,11,12]. We transplanted MSC immediately or 15 days after the injury.…”

Acute renal failure: definitions, diagnosis, pathogenesis, and therapy

“…Unfortunately, the beneficial effects of insulin-derived growth factor observed in experimental animals were not duplicated in a randomized study of patients with clinical ARF (88). A recent exciting approach in this area has been the administration of stem cells or endothelial cells to enhance recovery from acute ischemic renal injury in experimental animals (89)(90)(91)(92). There is ongoing research into the mechanisms whereby injured tubules are relined with new cells actively engaged in DNA synthesis.…”

Do Stem Cells Exist in the Adult Kidney?

“…There is evidence that bone marrow-derived cells can migrate to the kidney and form tubular epithelial cells following AKI [4,5,6,7,8]. However, the in vivo contribution of extrarenal cells to kidney regeneration is minimal [9,10,11].…”