Human Bone Marrow-mesenchymal Stem Cells Accelerate Recovery of Acute
Renal Injury and Prolong Survival in Mice
First published online May 22, 2008
* To whom correspondence should be addressed. E-mail:
morigi@marionegri.
Abstract
Transplantation of bone marrow mesenchymal stem cells or stromal
cells (BM-MSC) 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.
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AUTHOR CONTRIBUTIONS: M.M.: Conception and design, collection and/or
assembly of data, data analysis and interpretation, manuscript
writing.; M.I.: Conception and design, provision of study material or
patients, data analysis and interpretation.
design, collection and/or assembly of data, data analysis and
interpretation, manuscript writing.; D.C.: Data analysis and
interpretation.
analysis and interpretation, manuscript writing.; C.R.: Collection
and/or assembly of data, data analysis and interpretation.
Data analysis and interpretation.
collection and/or assembly of data, data analysis and interpretation,
final approval of manuscript.; N.P.: Collection and/or assembly of
data.; C.Z.: Collection and/or assembly of data, data analysis and
interpretation.
A.R.: Data analysis and interpretation, collection and/or assembly of
data.; G.R.: Conception and design, administrative support, data
analysis and interpretation, manuscript writing, final approval of
manuscript.
Marina Morigi, Martino Introna, Barbara Imberti contributed equally
to this work.
Key Words. human mesenchymal stem cells, acute renal failure, tubular
cells, kidney repair
Marina Morigi 1*, Martino Introna 2, Barbara Imberti 1, Daniela Corna
1, Mauro Abbate 1, Cinzia Rota 1, Daniela Rottoli 1, Ariela Benigni
1, Norberto Perico 1, Carla Zoja 1, Alessandro Rambaldi 2, Andrea
Remuzzi 1, Giuseppe Remuzzi 3
1 `Mario Negri' Institute for Pharmacological Research, Via Gavazzeni
11, 24125 Bergamo, Italy
2 Laboratorio di Terapia Cellulare e Genica "G. Lanzani", Unit of
Hematology, Azienda Ospedaliera, Ospedali Riuniti di Bergamo via
Garibaldi 11/13, 24, 24124 Bergamo, Italy
3 `Mario Negri' Institute for Pharmacological Research, Via Gavazzeni
11, 24125 Bergamo, Italy; Unit of Nephrology and Dialysis, Azienda
Ospedaliera, Ospedali Riuniti di Bergamo, Largo Barozzi 1, 24128
Bergamo, Italy
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