title: Mitochondrial transfer from bone-marrow-derived stromal cells to pulmonary alveoli protects against acute lung injury.
abstract: Bone marrow-derived stromal cells (BMSCs) protect against acute lung injury (ALI). To determine the role of BMSC mitochondria in this protection, we airway-instilled mice first with lipopolysaccharide (LPS) and then with either mouse BMSCs (mBMSCs) or human BMSCs (hBMSCs). Live optical studies revealed that the mBMSCs formed connexin 43 (Cx43)-containing gap junctional channels (GJCs) with the alveolar epithelia in these mice, releasing mitochondria-containing microvesicles that the epithelia engulfed. The presence of BMSC-derived mitochondria in the epithelia was evident optically, as well as by the presence of human mitochondrial DNA in mouse lungs instilled with hBMSCs. The mitochondrial transfer resulted in increased alveolar ATP concentrations. LPS-induced ALI, as indicated by alveolar leukocytosis and protein leak, inhibition of surfactant secretion and high mortality, was markedly abrogated by the instillation of wild-type mBMSCs but not of mutant, GJC-incompetent mBMSCs or mBMSCs with dysfunctional mitochondria. This is the first evidence, to our knowledge, that BMSCs protect against ALI by restituting alveolar bioenergetics through Cx43-dependent alveolar attachment and mitochondrial transfer.
authors.affiliation: Lung Biology Laboratory, Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, College of Physicians and Surgeons of Columbia University, New York, New York, USA.
authors.forename: Mohammad Naimul
authors.initials: MN
authors.lastname: Islam
authors.forename: Shonit R
authors.initials: SR
authors.lastname: Das
authors.forename: Memet T
authors.initials: MT
authors.lastname: Emin
authors.forename: Michelle
authors.initials: M
authors.lastname: Wei
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.forename: Kristin
authors.initials: K
authors.lastname: Westphalen
authors.forename: David J
authors.initials: DJ
authors.lastname: Rowlands
authors.forename: Sadiqa K
authors.initials: SK
authors.lastname: Quadri
authors.forename: Sunita
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: Jahar
authors.initials: J
authors.lastname: Bhattacharya
mesh_terms: D055371:Acute Lung Injury / Q000517:prevention & control*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology*; D018031:Connexin 43 / Q000502:physiology; D004734:Energy Metabolism; D017629:Gap Junctions / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000502:physiology*; D011650:Pulmonary Alveoli / Q000378:metabolism*; D017154:Stromal Cells / Q000502:physiology
chemical_list: D018031:Connexin 43; D000255:Adenosine Triphosphate