Life-sparing effect of human cord blood-mesenchymal stem cells in experimental acute kidney injury

Stem Cells. 2010 Mar 31;28(3):513-22. doi: 10.1002/stem.293.

Abstract

In search for new sources of mesenchymal stem cells (MSCs) for renal repair in acute kidney injury (AKI), we investigated the potential of human cord blood (CB)-MSCs to cure mice with AKI. Infusion of CB-MSCs in immunodeficient mice with cisplatin-induced AKI ameliorated both renal function and tubular cell injury, and prolonged survival. Transplanted CB-MSCs localized in peritubular areas, limited capillary alterations and neutrophil infiltration. Apoptosis reduced and tubular cell proliferation increased by virtue of stem cell capacity to produce growth factors. The reno-protective effect of CB-MSCs was further confirmed by their ability to inhibit oxidative damage and to induce the prosurvival factor Akt in tubular cells. The evidence that CB-MSCs in vitro increased the production of growth factors and inhibited IL-1 beta and TNFalpha synthesis when cocultured with damaged proximal tubular cells indicates a regenerative and anti-inflammatory action of stem cell treatment. Altogether these results highlight the potential of human CB-MSCs as future cell therapy for testing in human AKI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Anti-Inflammatory Agents / metabolism
  • Apoptosis / physiology
  • Cell Culture Techniques
  • Cell Differentiation / physiology*
  • Cell Proliferation
  • Coculture Techniques
  • Cord Blood Stem Cell Transplantation / methods*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Female
  • Graft Survival / physiology*
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Kidney / pathology
  • Kidney / physiopathology
  • Kidney / surgery*
  • Kidney Diseases / physiopathology
  • Kidney Diseases / surgery*
  • Kidney Tubules / cytology
  • Kidney Tubules / metabolism
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Mice, SCID
  • Oxidative Stress / physiology
  • Proto-Oncogene Proteins c-akt / metabolism

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Intercellular Signaling Peptides and Proteins
  • Proto-Oncogene Proteins c-akt