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Stem Cell Res Ther. 2015 May 22;6:102. doi: 10.1186/s13287-015-0093-2.

Mesenchymal stromal cell therapy attenuated lung and kidney injury but not brain damage in experimental cerebral malaria.

Author information

1
Laboratory of Applied Pharmacology, Farmanguinhos, Oswaldo Cruz Foundation, Av Brasil, 4365, Manguinhos, CEP-21040-900, Rio de Janeiro, RJ, Brazil. marianasouza@fiocruz.br.
2
Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Av Carlos Chagas Filho, 373 Bloco G, Cidade Universitária, CEP-21941-902, Rio de Janeiro, RJ, Brazil. johnatasdutra@gmail.com.
3
Laboratory of Applied Pharmacology, Farmanguinhos, Oswaldo Cruz Foundation, Av Brasil, 4365, Manguinhos, CEP-21040-900, Rio de Janeiro, RJ, Brazil. tatiana.ap2@gmail.com.
4
Laboratory of Applied Pharmacology, Farmanguinhos, Oswaldo Cruz Foundation, Av Brasil, 4365, Manguinhos, CEP-21040-900, Rio de Janeiro, RJ, Brazil. nattorres@globo.com.
5
Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Av Carlos Chagas Filho, 373 Bloco G, Cidade Universitária, CEP-21941-902, Rio de Janeiro, RJ, Brazil. maryantunes@gmail.com.
6
Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Av Carlos Chagas Filho, 373 Bloco G, Cidade Universitária, CEP-21941-902, Rio de Janeiro, RJ, Brazil. deboraxisto@gmail.com.
7
Laboratory of Biochemistry and Cellular Signaling, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Av Carlos Chagas Filho, 373 Bloco G, Cidade Universitária, CEP-21941-902, Rio de Janeiro, RJ, Brazil. thiagoswin@hotmail.com.
8
Department of Pathology, Faculty of Medicine, University of São Paulo, Av. Dr. Arnaldo, 455, Cerqueira César, CEP-01246903, São Paulo, SP, Brazil. vcapelozzi@lim05.fm.usp.br.
9
Laboratory of Cellular and Molecular Physiology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Av Carlos Chagas Filho, 373 Bloco G, Cidade Universitária, CEP-21941-902, Rio de Janeiro, RJ, Brazil. mmorales@biof.ufrj.br.
10
Laboratory of Biochemistry and Cellular Signaling, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Av Carlos Chagas Filho, 373 Bloco G, Cidade Universitária, CEP-21941-902, Rio de Janeiro, RJ, Brazil. acacia@biof.ufrj.br.
11
Laboratory of Biochemistry and Cellular Signaling, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Av Carlos Chagas Filho, 373 Bloco G, Cidade Universitária, CEP-21941-902, Rio de Janeiro, RJ, Brazil. caruso@biof.ufrj.br.
12
Laboratory of Applied Pharmacology, Farmanguinhos, Oswaldo Cruz Foundation, Av Brasil, 4365, Manguinhos, CEP-21040-900, Rio de Janeiro, RJ, Brazil. gracahenriques@fiocruz.br.
13
National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Oswaldo Cruz Foundation (Fiocruz), Av Brasil, 4365, Manguinhos, CEP-21040-900, Rio de Janeiro, RJ, Brazil. gracahenriques@fiocruz.br.
14
Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Av Carlos Chagas Filho, 373 Bloco G, Cidade Universitária, CEP-21941-902, Rio de Janeiro, RJ, Brazil. prmrocco@biof.ufrj.br.

Abstract

INTRODUCTION:

Malaria is the most relevant parasitic disease worldwide, and still accounts for 1 million deaths each year. Since current antimalarial drugs are unable to prevent death in severe cases, new therapeutic strategies have been developed. Mesenchymal stromal cells (MSC) confer host resistance against malaria; however, thus far, no study has evaluated the therapeutic effects of MSC therapy on brain and distal organ damage in experimental cerebral malaria.

METHODS:

Forty C57BL/6 mice were injected intraperitoneally with 5 × 10(6) Plasmodium berghei-infected erythrocytes or saline. After 24 h, mice received saline or bone marrow (BM)-derived MSC (1x10(5)) intravenously and were housed individually in metabolic cages. After 4 days, lung and kidney morphofunction; cerebrum, spleen, and liver histology; and markers associated with inflammation, fibrogenesis, and epithelial and endothelial cell damage in lung tissue were analyzed.

RESULTS:

In P. berghei-infected mice, BM-MSCs: 1) reduced parasitemia and mortality; 2) increased phagocytic neutrophil content in brain, even though BM-MSCs did not affect the inflammatory process; 3) decreased malaria pigment detection in spleen, liver, and kidney; 4) reduced hepatocyte derangement, with an increased number of Kupffer cells; 5) decreased kidney damage, without effecting significant changes in serum creatinine levels or urinary flow; and 6) reduced neutrophil infiltration, interstitial edema, number of myofibroblasts within interstitial tissue, and collagen deposition in lungs, resulting in decreased lung static elastance. These morphological and functional changes were not associated with changes in levels of tumor necrosis factor-α, keratinocyte-derived chemokine (KC, a mouse analog of interleukin-8), or interferon-γ, which remained increased and similar to those of P. berghei animals treated with saline. BM-MSCs increased hepatocyte growth factor but decreased VEGF in the P. berghei group.

CONCLUSIONS:

BM-MSC treatment increased survival and reduced parasitemia and malaria pigment accumulation in spleen, liver, kidney, and lung, but not in brain. The two main organs associated with worse prognosis in malaria, lung and kidney, sustained less histological damage after BM-MSC therapy, with a more pronounced improvement in lung function.

PMID:
25998168
PMCID:
PMC4462088
DOI:
10.1186/s13287-015-0093-2
[Indexed for MEDLINE]
Free PMC Article

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