Cited by 47Mesenchymal stem cell researchMitochondrial Function and PathologyAutophagy in Disease and Therapy

Therapeutic Effects of Mesenchymal Stromal Cells Require Mitochondrial Transfer and Quality Control

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Mukkala, Avinash Naraiah, Jerkic, Mirjana, Khan, Zahra, Szaszi, Katalin, Kapus, Andras, Rotstein, Ori·2023·International Journal of Molecular Sciences

Abstract

Due to their beneficial effects in an array of diseases, Mesenchymal Stromal Cells (MSCs) have been the focus of intense preclinical research and clinical implementation for decades. MSCs have multilineage differentiation capacity, support hematopoiesis, secrete pro-regenerative factors and exert immunoregulatory functions promoting homeostasis and the resolution of injury/inflammation. The main effects of MSCs include modulation of immune cells (macrophages, neutrophils, and lymphocytes), secretion of antimicrobial peptides, and transfer of mitochondria (Mt) to injured cells. These actions can be enhanced by priming (i.e., licensing) MSCs prior to exposure to deleterious microenvironments. Preclinical evidence suggests that MSCs can exert therapeutic effects in a variety of pathological states, including cardiac, respiratory, hepatic, renal, and neurological diseases. One of the key emerging beneficial actions of MSCs is the improvement of mitochondrial functions in the injured tissues by enhancing mitochondrial quality control (MQC). Recent advances in the understanding of cellular MQC, including mitochondrial biogenesis, mitophagy, fission, and fusion, helped uncover how MSCs enhance these processes. Specifically, MSCs have been suggested to regulate peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC1α)-dependent biogenesis, Parkin-dependent mitophagy, and Mitofusins (Mfn1/2) or Dynamin Related Protein-1 (Drp1)-mediated fission/fusion. In addition, previous studies also verified mitochondrial transfer from MSCs through tunneling nanotubes and via microvesicular transport. Combined, these effects improve mitochondrial functions, thereby contributing to the resolution of injury and inflammation. Thus, uncovering how MSCs affect MQC opens new therapeutic avenues for organ injury, and the transplantation of MSC-derived mitochondria to injured tissues might represent an attractive new therapeutic approach.

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Authors
Mukkala, A. N., Jerkic, M., Khan, Z., Szaszi, K., Kapus, A., & Rotstein, O.
Affiliations
  • St. Michael's Hospital (CA)
  • Unity Health Toronto, The Keenan Research Centre for Biomedical Science of St. Michael’s Hospital, University of Toronto, Toronto, ON M5B 1T8, Canada
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2023-10-31
Volume
24
Issue
21
Pages
15788
ISSN
1422-0067 (ISSN-L)
OpenAlex
W4388048619
Cited by
45
References
233
Citations by year
2026: 10 · 2025: 19 · 2024: 16
FWCI
2.12
Type
journal article
Language
en
Open access
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • TSpace (University of Toronto) (submittedVersion, cc-by)
Funders
  • Canadian Institutes of Health Research (CIHR) (#23766, PJT-180624, PJT-178152, AK2023)
  • Kidney Foundation of Canada (#23766, PJT-180624, PJT-178152, AK2023)
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 › Epidemiology › Autophagy in Disease and Therapy
Keywords
mesenchymal stem cells, mitochondrial transfer, mitochondrial quality control, mitophagy, mitochondrial biogenesis, mitochondrial fission and fusion, PGC-1α, Parkin, mitofusins, Drp1, tunneling nanotubes, extracellular vesicles, organ damage, inflammation resolution, immunomodulation
MeSH terms
Humans, Inflammation, Mitochondria, Cell Membrane Structures, Nanotubes, Mesenchymal Stem Cells

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