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https://www.arca.fiocruz.br/handle/icict/59381
MESENCHYMAL STROMAL CELL THERAPY ATTENUATED LUNG AND KIDNEY INJURY BUT NOT BRAIN DAMAGE IN EXPERIMENTAL CEREBRAL MALARIA
Experimental allergic-asthma
Stem-cells
Alzheimers-disease
Mononuclear-cells
Immune-responses
Mice
Sepsis
Model
Animal
Malaria
Male
Disease models
Inbred c57bl
Lung
Cultured
Plasmodium berghei
Cells
Lung injury
Cerebral
Acute kidney injury
Bone marrow cells
Kidney
Kupffer cells
Mesenchymal stem cell transplantation
Mesenchymal stromal cells
Survival rate
Author
Affilliation
Oswaldo Cruz Foundation. Institute of Technology in Pharmaceuticals - Farmanguinhos. Laboratory of Applied Pharmacology. Rio de Janeiro, RJ, Brazil.
Federal University of Rio de Janeiro. Carlos Chagas Filho Institute of Biophysics. Laboratory of Pulmonary Investigation. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. Institute of Technology in Pharmaceuticals - Farmanguinhos. Laboratory of Applied Pharmacology. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. Institute of Technology in Pharmaceuticals - Farmanguinhos. Laboratory of Applied Pharmacology. Rio de Janeiro, RJ, Brazil.
Federal University of Rio de Janeiro. Carlos Chagas Filho Institute of Biophysics. Laboratory of Pulmonary Investigation. Rio de Janeiro, RJ, Brazil.
Federal University of Rio de Janeiro. Carlos Chagas Filho Institute of Biophysics. Laboratory of Pulmonary Investigation. Rio de Janeiro, RJ, Brazil.
Federal University of Rio de Janeiro. Carlos Chagas Filho Institute of Biophysics. Laboratory of Biochemistry and Cellular Signaling. Rio de Janeiro, RJ, Brazil.
University of São Paulo. Faculty of Medicine. Department of Pathology. São Paulo, SP, Brazil.
Federal University of Rio de Janeiro. Carlos Chagas Filho Institute of Biophysics. Laboratory of Biochemistry and Cellular Signaling. Rio de Janeiro, RJ, Brazil.
Federal University of Rio de Janeiro. Carlos Chagas Filho Institute of Biophysics. Laboratory of Biochemistry and Cellular Signaling. Rio de Janeiro, RJ, Brazil.
Federal University of Rio de Janeiro. Carlos Chagas Filho Institute of Biophysics. Laboratory of Biochemistry and Cellular Signaling. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. Center for Technological Development in Health. National Institute for Science and Technology on Innovation on Neglected Diseases. Rio de Janeiro, RJ, Brazil / Oswaldo Cruz Foundation. Institute of Technology in Pharmaceuticals - Farmanguinhos. Laboratory of Applied Pharmacology. Rio de Janeiro, RJ, Brazil
Federal University of Rio de Janeiro. Carlos Chagas Filho Institute of Biophysics. Laboratory of Pulmonary Investigation. Rio de Janeiro, RJ, Brazil.
Federal University of Rio de Janeiro. Carlos Chagas Filho Institute of Biophysics. Laboratory of Pulmonary Investigation. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. Institute of Technology in Pharmaceuticals - Farmanguinhos. Laboratory of Applied Pharmacology. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. Institute of Technology in Pharmaceuticals - Farmanguinhos. Laboratory of Applied Pharmacology. Rio de Janeiro, RJ, Brazil.
Federal University of Rio de Janeiro. Carlos Chagas Filho Institute of Biophysics. Laboratory of Pulmonary Investigation. Rio de Janeiro, RJ, Brazil.
Federal University of Rio de Janeiro. Carlos Chagas Filho Institute of Biophysics. Laboratory of Pulmonary Investigation. Rio de Janeiro, RJ, Brazil.
Federal University of Rio de Janeiro. Carlos Chagas Filho Institute of Biophysics. Laboratory of Biochemistry and Cellular Signaling. Rio de Janeiro, RJ, Brazil.
University of São Paulo. Faculty of Medicine. Department of Pathology. São Paulo, SP, Brazil.
Federal University of Rio de Janeiro. Carlos Chagas Filho Institute of Biophysics. Laboratory of Biochemistry and Cellular Signaling. Rio de Janeiro, RJ, Brazil.
Federal University of Rio de Janeiro. Carlos Chagas Filho Institute of Biophysics. Laboratory of Biochemistry and Cellular Signaling. Rio de Janeiro, RJ, Brazil.
Federal University of Rio de Janeiro. Carlos Chagas Filho Institute of Biophysics. Laboratory of Biochemistry and Cellular Signaling. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. Center for Technological Development in Health. National Institute for Science and Technology on Innovation on Neglected Diseases. Rio de Janeiro, RJ, Brazil / Oswaldo Cruz Foundation. Institute of Technology in Pharmaceuticals - Farmanguinhos. Laboratory of Applied Pharmacology. Rio de Janeiro, RJ, Brazil
Federal University of Rio de Janeiro. Carlos Chagas Filho Institute of Biophysics. Laboratory of Pulmonary Investigation. Rio de Janeiro, RJ, Brazil.
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.
Keywords
Respiratory-distress-syndromeExperimental allergic-asthma
Stem-cells
Alzheimers-disease
Mononuclear-cells
Immune-responses
Mice
Sepsis
Model
Animal
Malaria
Male
Disease models
Inbred c57bl
Lung
Cultured
Plasmodium berghei
Cells
Lung injury
Cerebral
Acute kidney injury
Bone marrow cells
Kidney
Kupffer cells
Mesenchymal stem cell transplantation
Mesenchymal stromal cells
Survival rate
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