Artificial mitochondrial transplantation (AMT) reverses aging of mesenchymal stem cells and improves their immunomodulatory properties in LPS-induced synoviocytes inflammation.
Abstract: Nowadays, regenerative medicine techniques are usually based on the application of mesenchymal stem cells (MSCs) for the repair or restoration of injured damaged tissues. However, the effectiveness of autologous therapy is limited as therapeutic potential of MSCs declines due to patient's age, health condition and prolonged in vitro cultivation as a result of decreased growth rate. For that reason, there is an urgent need to develop strategies enabling the in vitro rejuvenation of MSCs prior transplantation in order to enhance their in vivo therapeutic efficiency. In presented study, we attempted to mimic the naturally occurring mitochondrial transfer (MT) between neighbouring cells and verify whether artificial MT (AMT) could reverse MSCs aging and improve their biological properties. For that reason, mitochondria were isolated from healthy donor equine adipose-derived stromal cells (ASCs) and transferred into metabolically impaired recipient ASCs derived from equine metabolic syndrome (EMS) affected horses, which were subsequently subjected to various analytical methods in order to verify the cellular and molecular outcomes of the applied AMT. Mitochondria recipient cells were characterized by decreased apoptosis, senescence and endoplasmic reticulum stress while insulin sensitivity was enhanced. Furthermore, we observed increased mitochondrial fragmentation and associated PARKIN protein accumulation, which indicates on the elimination of dysfunctional organelles via mitophagy. AMT further promoted physioxia and regulated autophagy fluxes. Additionally, rejuvenated ASCs displayed an improved anti-inflammatory activity toward LPS-stimulated synoviocytes. The presented findings highlight AMT as a promising alternative and effective method for MSCs rejuvenation, for potential application in autologous therapies in which MSCs properties are being strongly deteriorated due to patients' condition.
Copyright © 2024. Published by Elsevier B.V.
Publication Date: 2024-08-02 PubMed ID: 39098401DOI: 10.1016/j.bbamcr.2024.119806Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
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This research investigates whether artificially transplanting mitochondria can rejuvenate Mesenchymal stem cells (MSCs), which have seen reduced therapeutic efficiency due to age, health condition, and growth rate decline. Studies using equine adipose-derived stromal cells (ASCs) revealed that ASCs receiving new mitochondria showed characteristics of decreased cell death and aging, improved insulin sensitivity, and better anti-inflammatory activity. The results suggest that artificial mitochondrial transplantation (AMT) may be a viable method for renewing the therapeutic viability of MSCs in patients.
Relevance of Mesenchymal Stem Cells (MSCs) to Regenerative Medicine
- Mesenchymal stem cells play a crucial role in regenerative medicine techniques, which aim to repair or restore injured or damaged tissues.
- However, issues relating to the patient’s age, health condition, and a decrease in MSC growth rates limit the effectiveness of autologous therapy, which uses the patients’ own cells for treatment.
Concept of Artificial Mitochondrial Transplantation (AMT)
- The research team sought to devise a strategy that would rejuvenate MSCs, thereby improving their therapeutic efficiency.
- In nature, mitochondrial transfer occurs between neighboring cells. The researchers attempted to mimic this process artificially in an approach they termed AMT.
- In the AMT experiment, mitochondria were isolated from healthy donor equine adipose-derived stromal cells (ASCs) and transferred to metabolically impaired recipient ASCs derived from horses affected by equine metabolic syndrome (EMS).
Results and Outcomes of AMT
- Following AMT, the recipient cells showed a decrease in apoptosis (cell death) and senescence (aging). They also exhibited lower endoplasmic reticulum stress and improved insulin sensitivity.
- Other results included an increase in mitochondrial fragmentation and associated PARKIN protein accumulation, indicating the elimination of dysfunctional organelles via the process of mitophagy – the selective degradation of mitochondria by autophagy.
- AMT also promoted physioxia, which refers to the physical state of having the optimal concentration of oxygen, and managed autophagy fluxes or the dynamics of autophagy activity.
- Importantly, the rejuvenated ASCs showed advances in their anti-inflammatory activity when introduced to LPS-stimulated synoviocytes, the cells that line the joints.
Significance of the Study
- These findings point to AMT as a potentially effective method for rejuvenating MSCs, this could drastically enhance the efficacy of autologous therapies.
- For patients whose MSCs have declined significantly due to their health condition, AMT could offer a significant improvement to their therapeutic prospects.
Cite This Article
APA
Bourebaba L, Bourebaba N, Galuppo L, Marycz K.
(2024).
Artificial mitochondrial transplantation (AMT) reverses aging of mesenchymal stem cells and improves their immunomodulatory properties in LPS-induced synoviocytes inflammation.
Biochim Biophys Acta Mol Cell Res, 119806.
https://doi.org/10.1016/j.bbamcr.2024.119806 Publication
Researcher Affiliations
- Department of Experimental Biology, Wroclaw University of Environmental and Life Sciences, Norwida 27B, 50-375 Wroclaw, Poland. Electronic address: lynda.bourebaba@upwr.edu.pl.
- Department of Experimental Biology, Wroclaw University of Environmental and Life Sciences, Norwida 27B, 50-375 Wroclaw, Poland.
- Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, CA 95516, United States.
- Department of Experimental Biology, Wroclaw University of Environmental and Life Sciences, Norwida 27B, 50-375 Wroclaw, Poland; Department of Veterinary Medicine and Epidemiology, Veterinary Institute for Regenerative Cures, School of Veterinary Medicine, University of California, Davis, CA 95516, United States. Electronic address: krzysztof.marycz@upwr.edu.pl.
Conflict of Interest Statement
Declaration of competing interest The authors confirm that there are no conflicts of interest.
Citations
This article has been cited 3 times.- Ma J, Wang X, Sun D, Chen J, Zhou L, Zou K, Ni X, Jin H, Lin J. DPSCs modulate synovial macrophage polarization and efferocytosis via PINK1/Parkin-dependent mitophagy. Stem Cell Res Ther 2025 Jul 9;16(1):356.
- Kubat GB, Picone P, Tuncay E, Aryan L, Girgenti A, Palumbo L, Turkel I, Akat F, Singh KK, Nuzzo D. Biotechnological approaches and therapeutic potential of mitochondria transfer and transplantation. Nat Commun 2025 Jul 1;16(1):5709.
- Zhang M, Wu J, Cai K, Liu Y, Lu B, Zhang J, Xu J, Gu C, Chen T. From dysfunction to healing: advances in mitochondrial therapy for Osteoarthritis. J Transl Med 2024 Nov 11;22(1):1013.
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