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Review

Mesenchymal Stromal Cells and Extracellular Vesicles: A Novel Therapeutic Paradigm for Mitochondrial Dysfunctions

by
Eman Salem Algariri
1,
Fazlina Nordin
1,*,
Min Hwei Ng
1,
Izyan Mohd Idris
2,
Norwahidah Abdul Karim
3,
Gee Jun Tye
4,5 and
Wan Safwani Wan Kamarul Zaman
6
1
Department of Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia
2
Institute for Medical Research (IMR), National Institutes of Health (NIH), Ministry of Health Malaysia, Shah Alam 40170, Selangor, Malaysia
3
Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia
4
Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Minden 11800, Penang, Malaysia
5
Malaysian Institute of Pharmaceuticals and Nutraceuticals, National Institutes of Biotechnology Malaysia, Gelugor 11700, Penang, Malaysia
6
Department of Pharmaceutical Life Sciences, Faculty of Pharmacy, Universiti Malaya, Kuala Lumpur 50603, Malaysia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2026, 27(4), 1981; https://doi.org/10.3390/ijms27041981
Submission received: 23 December 2025 / Revised: 4 February 2026 / Accepted: 9 February 2026 / Published: 19 February 2026
(This article belongs to the Special Issue Current Insights into the Role of Exosomes in Intercellular Communication, 2nd Edition)
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Abstract

Mitochondrial dysfunction is a central pathological feature of a wide range of inherited and acquired disorders and is characterized by impaired oxidative phosphorylation, disrupted cellular energy metabolism, and excessive oxidative stress. Although advances in molecular diagnostics have improved disease recognition, effective disease-modifying therapies remain limited, and clinical outcomes are often suboptimal, highlighting the need for novel therapeutic strategies. Mesenchymal stromal cells (MSCs) and their extracellular vesicles (MSC-EVs) have emerged as promising candidates for targeting mitochondrial dysfunction due to their regenerative, immunomodulatory, and metabolic regulatory properties. In this review, we provide a comprehensive overview of recent in vitro and in vivo studies investigating the capacity of MSCs and MSC-EVs to restore mitochondrial function by enhancing mitochondrial respiration, improving cellular bioenergetics, and reducing oxidative stress across diverse disease models. We further discuss the underlying mechanisms involved, including mitochondrial transfer, delivery of functional mitochondrial components, and modulation of the cellular microenvironment. Finally, we highlight the key advantages, translational potential, and remaining challenges associated with MSC- and MSC-EV-based therapies for mitochondrial dysfunction.
Keywords: mitochondrial diseases; mitochondrial transfer; oxidative phosphorylation; MSC-base therapy; MSC-EVs; exosomes mitochondrial diseases; mitochondrial transfer; oxidative phosphorylation; MSC-base therapy; MSC-EVs; exosomes
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MDPI and ACS Style

Algariri, E.S.; Nordin, F.; Ng, M.H.; Mohd Idris, I.; Abdul Karim, N.; Tye, G.J.; Wan Kamarul Zaman, W.S. Mesenchymal Stromal Cells and Extracellular Vesicles: A Novel Therapeutic Paradigm for Mitochondrial Dysfunctions. Int. J. Mol. Sci. 2026, 27, 1981. https://doi.org/10.3390/ijms27041981

AMA Style

Algariri ES, Nordin F, Ng MH, Mohd Idris I, Abdul Karim N, Tye GJ, Wan Kamarul Zaman WS. Mesenchymal Stromal Cells and Extracellular Vesicles: A Novel Therapeutic Paradigm for Mitochondrial Dysfunctions. International Journal of Molecular Sciences. 2026; 27(4):1981. https://doi.org/10.3390/ijms27041981

Chicago/Turabian Style

Algariri, Eman Salem, Fazlina Nordin, Min Hwei Ng, Izyan Mohd Idris, Norwahidah Abdul Karim, Gee Jun Tye, and Wan Safwani Wan Kamarul Zaman. 2026. "Mesenchymal Stromal Cells and Extracellular Vesicles: A Novel Therapeutic Paradigm for Mitochondrial Dysfunctions" International Journal of Molecular Sciences 27, no. 4: 1981. https://doi.org/10.3390/ijms27041981

APA Style

Algariri, E. S., Nordin, F., Ng, M. H., Mohd Idris, I., Abdul Karim, N., Tye, G. J., & Wan Kamarul Zaman, W. S. (2026). Mesenchymal Stromal Cells and Extracellular Vesicles: A Novel Therapeutic Paradigm for Mitochondrial Dysfunctions. International Journal of Molecular Sciences, 27(4), 1981. https://doi.org/10.3390/ijms27041981

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