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Mitochondrial donation by mesenchymal stromal cells rescues alveolar surfactant secretion in sepsis
Author(s) -
Islam Mohammad Naimul,
Otsu Keishi,
Houser Sandra D.,
Lindert Jens,
Bhattacharya Jahar
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.612.24
Subject(s) - mesenchymal stem cell , pulmonary surfactant , secretion , chemistry , lung , mitochondrion , stromal cell , microbiology and biotechnology , pathology , biology , medicine , biochemistry
In sepsis, bone marrow derived mesenchymal stromal cells (MSCs) protect against acute lung injury (ALI). However, underlying mechanisms are unclear. We reported, MSCs transfer mitochondria to cultured capillaries (Otsu et al, 2008). To determine whether mitochondrial transfer occurs in situ , in anesthetized rats we intratracheally instilled lipopolysaccharide (LPS) or saline. After 4 hours, we instilled MSCs (2×10 6 cells) that expressed the mitochondria‐targeted fluorescent protein, DsRed. After 24 hours, we isolated and blood‐perfused the lungs. In alveoli viewed by confocal microscopy, we determined DsRed fluorescence and alveolar surfactant secretion in single type 2 (AT2) cells (Ashino et al, 2000). In saline‐treated lungs, no alveolar MSCs were evident. In LPS‐treated lungs, in some but not all alveoli MSCs adhered to alveolar epithelium (AE) and DsRed localized intracellularly in AT2 cells. Surfactant secretion stimulated by a 15‐second hyperinflation, was evident in alveoli containing MSCs, but not in MSC‐free alveoli. Our findings indicate that in LPS‐treated lungs (i) MSCs transfer mitochondria to AT2 cells, and that (ii) surfactant secretion is abrogated in MSC‐free alveoli, but protected in alveoli containing MSCs. MSC‐AEC mitochondrial transfer might increase ATP in AT2 cells, thereby rescuing surfactant secretion and protecting lung function in ALI (support HL64896 & HL57556).