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

By M. Islam, Shonita Das, M. Emin, M. Wei, L. Sun, Kristin Westphalen, D. Rowlands, S. Quadri, S. Bhattacharya, J. Bhattacharya. Nature Medicine, 2012

1,429 citations recorded by the source corpus.

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.

Subfields: Genetics, Pulmonary and Respiratory Medicine, Surgery

View Paper: https://www.semanticscholar.org/paper/35973e265a0324c1ffbbac413e7105fc3b0dfc1b

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In Genetics

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Citations in the corpus

• Mitochondrial dysfunction: mechanisms and advances in therapy (2024, background): “413,414 Moreover, mitochondrial restoration which bene fi ted from MSCs also protected epithelial cells from apoptosis in asthma.”
• Mitochondrial genome acquisition restores respiratory function and tumorigenic potential of cancer cells without mitochondrial DNA. (2015, background): “, 2008) and in a mouse model of acute lung injury, documenting mitochondrial transfer from mesenchymal stem cells (MSCs) injected into the animal’s lungs (Islam et al., 2012).”
• Mechanisms of mesenchymal stem/stromal cell function (2016, background): “Unlike wild-type MSCs, MSCs genetically modified for connexin 43 that were incapable of forming gap junctions and MSCs with dysfunctional mitochondria did not reduce acute lung injury [124].”
• Mitochondrial DNA in inflammation and immunity (2020, neutral): “Thirdly, mitochondria can be directly transferred between cells through connexin 43 gap junctions, as had been seen between bone marrow-derived stromal cells and pulmonary alveoli during lung injury [203].”
• Mesenchymal Stromal Cells Modulate Macrophages in Clinically Relevant Lung Injury Models by Extracellular Vesicle Mitochondrial Transfer (2017, background): “Am J Respir Crit Care Med 2017;195(9):1253-1263.”