Life-Sparing Effect of Human Cord Blood-Mesenchymal Stem Cells in Experimental Acute Kidney Injury

Author:

Morigi Marina1,Rota Cinzia1,Montemurro Tiziana2,Montelatici Elisa2,Lo Cicero Viviana2,Imberti Barbara1,Abbate Mauro1,Zoja Carla1,Cassis Paola1,Longaretti Lorena1,Rebulla Paolo2,Introna Martino3,Capelli Chiara3,Benigni Ariela1,Remuzzi Giuseppe13,Lazzari Lorenza2

Affiliation:

1. “Mario Negri” Institute for Pharmacological Research, Bergamo, Italy

2. Cell Factory, Centro di Medicina Trasfusionale, Terapia Cellulare e Criobiologia, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy

3. Laboratory of Cell Therapy “G. Lanzani,” Ospedali Riuniti di Bergamo, Bergamo, ItalyUnit of Hematology and Unit of Nephrology and Dialysis, Azienda Ospedaliera, Ospedali Riuniti di Bergamo, Bergamo, Italy

Abstract

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-1β and TNFα 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.

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,Molecular Medicine

Reference70 articles.

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