The DOI matches its Crossref record; 229 of the 233 references it cites were found in a registry or an index.
Therapeutic Effects of Mesenchymal Stromal Cells Require Mitochondrial Transfer and Quality Control
Open accessAbstract
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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“MSCs can engulf and degrade dysfunctional Mt released from injured cells [122].”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [122]
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“This process, in turn, boosts mitochondrial biogenesis within the MSCs, enhancing their capacity to donate functional Mt to recipient cells, thereby improving overall mitochondrial quality control (MQC) and metabolic function [122, 123].”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [122]
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Flagged first, then by citations
4 of the 233 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- Maumus, 2018, Mesenchymal Stem Cells and Regenerative Medicine: Future Perspectives in Osteoarthritis, Med. Sci., 34, 1092
Cited by
Sorted by citations
Tissue Engineering and Regenerative Medicine: Perspectives and Challenges
Hoang, V. T., Nguyen, Q. T., Phan, T. T. K., Pham, T. H., Dinh, N. T. H., Anh, L. P. H., Dao, L. T. M., Bui, V. D., Dao, H., Le, D. S., et al. (2025) · MedComm · doi:10.1002/mco2.70192 · Cited by 67
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Metadata
- 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)
- PMC
- PMC10647450
- 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
- gold
- doi.org
- Licence
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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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