Mitochondrial transfer from bone-marrow-derived stromal cells to pulmonary alveoli protects against acute lung injury

被引：1179

作者：

Islam, Mohammad Naimul ^{[1
]}

Das, Shonit R. ^{[1
]}

Emin, Memet T. ^{[1
]}

Wei, Michelle ^{[1
]}

Sun, Li ^{[1
]}

Westphalen, Kristin ^{[1
]}

Rowlands, David J. ^{[1
]}

Quadri, Sadiqa K. ^{[1
]}

Bhattacharya, Sunita ^{[1
]}

Bhattacharya, Jahar ^{[1
]}

机构：

[1] Columbia Univ Coll Phys & Surg, Dept Med, Div Pulm Allergy & Crit Care Med, Lung Biol Lab, New York, NY 10032 USA

来源：

NATURE MEDICINE | 2012年 / 18卷 / 05期

基金：

美国国家卫生研究院;

关键词：

MESENCHYMAL STEM-CELLS; DYSFUNCTION; ENGRAFTMENT; EXOCYTOSIS; SURFACTANT; SEVERITY; CONNEXIN; THERAPY; SEPSIS; ROS;

D O I：

10.1038/nm.2736

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：759 / U153

页数：8

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