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Cited by 582Mesenchymal stem cell researchMitochondrial Function and PathologyRespiratory Support and Mechanisms

Mitochondrial Transfer via Tunneling Nanotubes is an Important Mechanism by Which Mesenchymal Stem Cells Enhance Macrophage Phagocytosis in the In Vitro and In Vivo Models of ARDS

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Jackson, Megan V., Morrison, Thomas J., Doherty, Declan F., McAuley, Daniel F., Matthay, Michael A., Kissenpfennig, Adrien, O'Kane, Cecilia M., Krasnodembskaya, Anna D.·2016·Stem Cells
DOI 10.1002/stem.2372PMC PMC4982045
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Abstract

Mesenchymal stromal cells (MSC) have been reported to improve bacterial clearance in preclinical models of Acute Respiratory Distress Syndrome (ARDS) and sepsis. The mechanism of this effect is not fully elucidated yet. The primary objective of this study was to investigate the hypothesis that the antimicrobial effect of MSC in vivo depends on their modulation of macrophage phagocytic activity which occurs through mitochondrial transfer. We established that selective depletion of alveolar macrophages (AM) with intranasal (IN) administration of liposomal clodronate resulted in complete abrogation of MSC antimicrobial effect in the in vivo model of Escherichia coli pneumonia. Furthermore, we showed that MSC administration was associated with enhanced AM phagocytosis in vivo. We showed that direct coculture of MSC with monocyte-derived macrophages enhanced their phagocytic capacity. By fluorescent imaging and flow cytometry we demonstrated extensive mitochondrial transfer from MSC to macrophages which occurred at least partially through tunneling nanotubes (TNT)-like structures. We also detected that lung macrophages readily acquire MSC mitochondria in vivo, and macrophages which are positive for MSC mitochondria display more pronounced phagocytic activity. Finally, partial inhibition of mitochondrial transfer through blockage of TNT formation by MSC resulted in failure to improve macrophage bioenergetics and complete abrogation of the MSC effect on macrophage phagocytosis in vitro and the antimicrobial effect of MSC in vivo. Collectively, this work for the first time demonstrates that mitochondrial transfer from MSC to innate immune cells leads to enhancement in phagocytic activity and reveals an important novel mechanism for the antimicrobial effect of MSC in ARDS.

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Cited by

Sorted by citations

Authors
Jackson, M. V., Morrison, T. J., Doherty, D. F., McAuley, D. F., Matthay, M. A., Kissenpfennig, A., O'Kane, C. M., & Krasnodembskaya, A. D.
Affiliations
  • Queen's University Belfast (GB)
  • University of California, San Francisco (US)
  • Centre for Experimental Medicine, School of Medicine Dentistry & Biomedical Sciences, Queen's University Belfast, Northern Ireland, UK
Corresponding author
Krasnodembskaya, Anna D.
ORCID
Venue
Stem Cells
Publisher
Oxford University Press (OUP)
Published
2016-04-29
Volume
34
Issue
8
Pages
2210-2223
ISSN
  • 1066-5099 (ISSN-L)
  • 1549-4918
DOI
10.1002/stem.2372
PMC
PMC4982045
OpenAlex
W2336025467
Cited by
582
References
4
Citations by year
2026: 54 · 2025: 43 · 2024: 58 · 2023: 66 · 2022: 68 · 2021: 86 · 2020: 91 · 2019: 43 · 2018: 29 · 2017: 33 · 2016: 9 · 2014: 1
FWCI
27.57
Type
journal article
Language
en
Open access
Licence
Locations
  • Stem Cells (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • Research Portal (Queen's University Belfast) (submittedVersion, cc-by)
Funders
  • Texas A&M Health Science Center College of Medicine Institute for Regenerative Medicine at Scott & White (MRC MR/L017229/1, NHLBI HL51854 (MAM). Some of the materials employed in this work were provided by the)
  • NCRR (through a grant from)
  • NIH (of the, Grant # P40RR017447)
Topics
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory Support and Mechanisms
Keywords
mesenchymal stem cells, acute respiratory distress syndrome, tunneling nanotubes, mitochondrial transfer, macrophage phagocytosis, alveolar macrophages, Escherichia coli pneumonia, clodronate liposomes, macrophage depletion, antimicrobial activity, sepsis, innate immunity
MeSH terms
Animals, Anti-Infective Agents, Cell Communication, Cells, Cultured, Disease Models, Animal, Escherichia coli, Humans, Macrophages, Mitochondria, Neutrophils, Phagocytosis, Pneumonia, Respiratory Distress Syndrome, Macrophages, Alveolar, Coculture Techniques, Nanotubes, Mice, Mesenchymal Stem Cells

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