Tissue-Specific Stem Cells

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

  1. Marina Morigi1,‡,*,
  2. Cinzia Rota1,
  3. Tiziana Montemurro2,
  4. Elisa Montelatici2,
  5. Viviana Lo Cicero2,
  6. Barbara Imberti1,
  7. Mauro Abbate1,
  8. Carla Zoja1,
  9. Paola Cassis1,
  10. Lorena Longaretti1,
  11. Paolo Rebulla2,
  12. Martino Introna3,
  13. Chiara Capelli3,
  14. Ariela Benigni1,
  15. Giuseppe Remuzzi1,3,
  16. Lorenza Lazzari2

Article first published online: 4 JAN 2010

DOI: 10.1002/stem.293

Issue

STEM CELLS

STEM CELLS

Volume 28, Issue 3, pages 513–522, March 2010

Additional Information

How to Cite

Morigi, M., Rota, C., Montemurro, T., Montelatici, E., Lo Cicero, V., Imberti, B., Abbate, M., Zoja, C., Cassis, P., Longaretti, L., Rebulla, P., Introna, M., Capelli, C., Benigni, A., Remuzzi, G. and Lazzari, L. (2010), Life-Sparing Effect of Human Cord Blood-Mesenchymal Stem Cells in Experimental Acute Kidney Injury. STEM CELLS, 28: 513–522. doi: 10.1002/stem.293

Author Information

  1. 1

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

  2. 2

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

  3. 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

  1. ‡

    Telephone: +39-035-319-888; Fax: +39-035-319-331

*“Mario Negri” Institute for Pharmacological Research, Via Gavazzeni 11, 24125 Bergamo, Italy

  1. †

    Author contributions: M.M.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing; C.R.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing; T.M.: provision of study material, collection and/or assembly of data; E.M.: provision of study material, collection and/or assembly of data; V.L.C.: provision of study material, collection and/or assembly of data; B.I.: collection and/or assembly of data, data analysis and interpretation, manuscript writing; M.A.: collection and/or assembly of data, data analysis and interpretation, manuscript writing; C.Z.: collection and/or assembly of data, data analysis and interpretation; P.C.: collection and/or assembly of data; L. Longaretti: collection and/or assembly of data; P.R.: provision of study material, collection and/or assembly of data, data analysis and interpretation, final approval of manuscript; M.I.: provision of study material and data analysis and interpretation; C.C.: provision of study material; A.B.: conception and design, data analysis and interpretation, manuscript writing, final approval of manuscript; G.R.: conception and design, data analysis and interpretation, manuscript writing, final approval of manuscript; L. Lazzari: provision of study material, collection and/or assembly of data, data analysis and interpretation, final approval of manuscript. M.M. and C.R. contributed equally to this article.

  2. Disclosure of potential conflicts of interest is found at the end of this article.

  3. First published online in STEM CELLSEXPRESS January 4, 2010.

  4. ‡

    Telephone: +39-035-319-888; Fax: +39-035-319-331

Publication History

  1. Issue published online: 24 MAR 2010
  2. Article first published online: 4 JAN 2010
  3. Accepted manuscript online: 4 JAN 2010 12:00AM EST
  4. Manuscript Accepted: 22 DEC 2009
  5. Manuscript Received: 10 JUN 2009

Funded by

  • Fondazione Cariplo Milano, Italy. Grant Number: 2007-5549
  • Fondaazione Il Sangue
  • Ministero della Salute (Progetto a concorso 2009
  • Ricerca corrente 2008 e 2009
  • Istituto Superiore di Sanità (Malattie Neurodegenerative 2006)
  • Sixth FP “Thercord”. Grant Number: LHSB-CT-2006-018817
  • Seventh FP “CASCADE”, (Cultivated Adult Stem Cells as Alternative for Damaged Tissues). Grant Number: HEALTH-F5-2009-223236
  • European Community under the European Community's Seventh Framework Programme. Grant Numbers: FP7/2007-2013, 223007
  • STAR-TREK project

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Keywords:

  • Human cord blood-mesenchymal stem cells;
  • Acute renal failure;
  • Tubular cells;
  • Kidney repair

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. STEM CELLS 2010;28:513–522

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