Human bone marrow mesenchymal stem cells accelerate recovery of acute renal injury and prolong survival in mice

Marina Morigi, Martino Introna, Barbara Imberti, Daniela Corna, Mauro Abbate, Cinzia Rota, Daniela Rottoli, Ariela Benigni, Norberto Perico, Carla Zoja, Alessandro Rambaldi, Andrea Remuzzi, Giuseppe Remuzzia

Research output: Contribution to journalArticle

292 Citations (Scopus)

Abstract

Transplantation of bone marrow mesenchymal stem cells (BM-MSC) or stromal cells from rodents has been identified as a strategy for renal repair in experimental models of acute kidney injury (AKI), a highly life-threatening clinical setting. The therapeutic potential of BM-MSC of human origin has not been reported so far. Here, we investigated whether human BM-MSC treatment could prevent AKI induced by cisplatin and prolong survival in an immunodeficient mouse model. Results showed that human BM-MSC infusion decreased proximal tubular epithelial cell injury and ameliorated the deficit in renal function, resulting in reduced recipient mortality. Infused BM-MSC became localized predominantly in peritubular areas and acted to reduce renal cell apoptosis and to increase proliferation. BM-MSC also induced protection against AKI-related peritubular capillary changes consisting of endothelial cell abnormalities, leukocyte infiltration, and low endothelial cell and lumen volume density as assessed by morphometric analysis. These findings indicate that human MSC of bone marrow origin hold potential to prolong survival in AKI and should be considered for testing in a clinical trial.

Original languageEnglish
Pages (from-to)2075-2082
Number of pages8
JournalStem Cells
Volume26
Issue number8
DOIs
Publication statusPublished - Aug 2008

Fingerprint

Mesenchymal Stromal Cells
Acute Kidney Injury
Bone Marrow
Survival
Kidney
Endothelial Cells
Stromal Cells
Bone Marrow Transplantation
Cell Size
Cisplatin
Rodentia
Leukocytes
Theoretical Models
Epithelial Cells
Clinical Trials
Apoptosis
Mortality
Wounds and Injuries
Therapeutics

Keywords

  • Acute renal failure
  • Human mesenchymal stem cells
  • Kidney repair
  • Tubular cells

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine

Cite this

Human bone marrow mesenchymal stem cells accelerate recovery of acute renal injury and prolong survival in mice. / Morigi, Marina; Introna, Martino; Imberti, Barbara; Corna, Daniela; Abbate, Mauro; Rota, Cinzia; Rottoli, Daniela; Benigni, Ariela; Perico, Norberto; Zoja, Carla; Rambaldi, Alessandro; Remuzzi, Andrea; Remuzzia, Giuseppe.

In: Stem Cells, Vol. 26, No. 8, 08.2008, p. 2075-2082.

Research output: Contribution to journalArticle

Morigi, Marina ; Introna, Martino ; Imberti, Barbara ; Corna, Daniela ; Abbate, Mauro ; Rota, Cinzia ; Rottoli, Daniela ; Benigni, Ariela ; Perico, Norberto ; Zoja, Carla ; Rambaldi, Alessandro ; Remuzzi, Andrea ; Remuzzia, Giuseppe. / Human bone marrow mesenchymal stem cells accelerate recovery of acute renal injury and prolong survival in mice. In: Stem Cells. 2008 ; Vol. 26, No. 8. pp. 2075-2082.
@article{b630f31c70c24162b2ccda0bdc42aa49,
title = "Human bone marrow mesenchymal stem cells accelerate recovery of acute renal injury and prolong survival in mice",
abstract = "Transplantation of bone marrow mesenchymal stem cells (BM-MSC) or stromal cells from rodents has been identified as a strategy for renal repair in experimental models of acute kidney injury (AKI), a highly life-threatening clinical setting. The therapeutic potential of BM-MSC of human origin has not been reported so far. Here, we investigated whether human BM-MSC treatment could prevent AKI induced by cisplatin and prolong survival in an immunodeficient mouse model. Results showed that human BM-MSC infusion decreased proximal tubular epithelial cell injury and ameliorated the deficit in renal function, resulting in reduced recipient mortality. Infused BM-MSC became localized predominantly in peritubular areas and acted to reduce renal cell apoptosis and to increase proliferation. BM-MSC also induced protection against AKI-related peritubular capillary changes consisting of endothelial cell abnormalities, leukocyte infiltration, and low endothelial cell and lumen volume density as assessed by morphometric analysis. These findings indicate that human MSC of bone marrow origin hold potential to prolong survival in AKI and should be considered for testing in a clinical trial.",
keywords = "Acute renal failure, Human mesenchymal stem cells, Kidney repair, Tubular cells",
author = "Marina Morigi and Martino Introna and Barbara Imberti and Daniela Corna and Mauro Abbate and Cinzia Rota and Daniela Rottoli and Ariela Benigni and Norberto Perico and Carla Zoja and Alessandro Rambaldi and Andrea Remuzzi and Giuseppe Remuzzia",
year = "2008",
month = "8",
doi = "10.1634/stemcells.2007-0795",
language = "English",
volume = "26",
pages = "2075--2082",
journal = "Stem Cells",
issn = "1066-5099",
publisher = "AlphaMed Press",
number = "8",

}

TY - JOUR

T1 - Human bone marrow mesenchymal stem cells accelerate recovery of acute renal injury and prolong survival in mice

AU - Morigi, Marina

AU - Introna, Martino

AU - Imberti, Barbara

AU - Corna, Daniela

AU - Abbate, Mauro

AU - Rota, Cinzia

AU - Rottoli, Daniela

AU - Benigni, Ariela

AU - Perico, Norberto

AU - Zoja, Carla

AU - Rambaldi, Alessandro

AU - Remuzzi, Andrea

AU - Remuzzia, Giuseppe

PY - 2008/8

Y1 - 2008/8

N2 - Transplantation of bone marrow mesenchymal stem cells (BM-MSC) or stromal cells from rodents has been identified as a strategy for renal repair in experimental models of acute kidney injury (AKI), a highly life-threatening clinical setting. The therapeutic potential of BM-MSC of human origin has not been reported so far. Here, we investigated whether human BM-MSC treatment could prevent AKI induced by cisplatin and prolong survival in an immunodeficient mouse model. Results showed that human BM-MSC infusion decreased proximal tubular epithelial cell injury and ameliorated the deficit in renal function, resulting in reduced recipient mortality. Infused BM-MSC became localized predominantly in peritubular areas and acted to reduce renal cell apoptosis and to increase proliferation. BM-MSC also induced protection against AKI-related peritubular capillary changes consisting of endothelial cell abnormalities, leukocyte infiltration, and low endothelial cell and lumen volume density as assessed by morphometric analysis. These findings indicate that human MSC of bone marrow origin hold potential to prolong survival in AKI and should be considered for testing in a clinical trial.

AB - Transplantation of bone marrow mesenchymal stem cells (BM-MSC) or stromal cells from rodents has been identified as a strategy for renal repair in experimental models of acute kidney injury (AKI), a highly life-threatening clinical setting. The therapeutic potential of BM-MSC of human origin has not been reported so far. Here, we investigated whether human BM-MSC treatment could prevent AKI induced by cisplatin and prolong survival in an immunodeficient mouse model. Results showed that human BM-MSC infusion decreased proximal tubular epithelial cell injury and ameliorated the deficit in renal function, resulting in reduced recipient mortality. Infused BM-MSC became localized predominantly in peritubular areas and acted to reduce renal cell apoptosis and to increase proliferation. BM-MSC also induced protection against AKI-related peritubular capillary changes consisting of endothelial cell abnormalities, leukocyte infiltration, and low endothelial cell and lumen volume density as assessed by morphometric analysis. These findings indicate that human MSC of bone marrow origin hold potential to prolong survival in AKI and should be considered for testing in a clinical trial.

KW - Acute renal failure

KW - Human mesenchymal stem cells

KW - Kidney repair

KW - Tubular cells

UR - http://www.scopus.com/inward/record.url?scp=55049087497&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=55049087497&partnerID=8YFLogxK

U2 - 10.1634/stemcells.2007-0795

DO - 10.1634/stemcells.2007-0795

M3 - Article

VL - 26

SP - 2075

EP - 2082

JO - Stem Cells

JF - Stem Cells

SN - 1066-5099

IS - 8

ER -