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2015 ; 6
(1
): 102
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Mesenchymal stromal cell therapy attenuated lung and kidney injury but not brain
damage in experimental cerebral malaria
#MMPMID25998168
Souza MC
; Silva JD
; Pádua TA
; Torres ND
; Antunes MA
; Xisto DG
; Abreu TP
; Capelozzi VL
; Morales MM
; Sá Pinheiro AA
; Caruso-Neves C
; Henriques MG
; Rocco PR
Stem Cell Res Ther
2015[May]; 6
(1
): 102
PMID25998168
show ga
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-?,
keratinocyte-derived chemokine (KC, a mouse analog of interleukin-8), or
interferon-?, 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.