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Mesenchymal stem cell-mediated transfer of mitochondria: mechanisms and functional impact

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Abstract

There is a steadily growing interest in the use of mitochondria as therapeutic agents. The use of mitochondria derived from mesenchymal stem/stromal cells (MSCs) for therapeutic purposes represents an innovative approach to treat many diseases (immune deregulation, inflammation-related disorders, wound healing, ischemic events, and aging) with an increasing amount of promising evidence, ranging from preclinical to clinical research. Furthermore, the eventual reversal, induced by the intercellular mitochondrial transfer, of the metabolic and pro-inflammatory profile, opens new avenues to the understanding of diseases’ etiology, their relation to both systemic and local risk factors, and also leads to new therapeutic tools for the control of inflammatory and degenerative diseases. To this end, we illustrate in this review, the triggers and mechanisms behind the transfer of mitochondria employed by MSCs and the underlying benefits as well as the possible adverse effects of MSCs mitochondrial exchange. We relay the rationale and opportunities for the use of these organelles in the clinic as cell-based product.

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Funding

This work was supported by grants from the Chilean National Agency for Investigation and Development: ANID (Agencia Nacional de Investigación y Desarrollo) FONDECYT Regular #1211749 and FONDECYT de Iniciación #11221017, and by ANID—Basal funding for Scientific and Technological Center of Excellence, IMPACT, #FB210024.

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Authors and Affiliations

  1. IMPACT, Center of Interventional Medicine for Precision and Advanced Cellular Therapy, Santiago, Chile

    Francesca Velarde, Sarah Ezquerra, Xavier Delbruyere, Yessia Hidalgo & Maroun Khoury

  2. Laboratory of Nano-Regenerative Medicine, Faculty of Medicine, Universidad de los Andes, Santiago, Chile

    Francesca Velarde, Sarah Ezquerra, Xavier Delbruyere, Yessia Hidalgo & Maroun Khoury

  3. Cells for Cells and REGENERO, The Chilean Consortium for Regenerative Medicine, Santiago, Chile

    Francesca Velarde, Sarah Ezquerra, Xavier Delbruyere, Yessia Hidalgo & Maroun Khoury

  4. Universidad San Francisco de Quito USFQ, Colegio de Ciencias de la Salud, Escuela de Medicina, Quito, Ecuador

    Andres Caicedo

  5. Universidad San Francisco de Quito USFQ, Instituto de Investigaciones en Biomedicina iBioMed, Quito, Ecuador

    Andres Caicedo

  6. Mito-Act Research Consortium, Quito, Ecuador

    Andres Caicedo

  7. Sistemas Médicos SIME, Universidad San Francisco de Quito USFQ, Quito, Ecuador

    Andres Caicedo

  8. Faculty of Medicine, Universidad de los Andes, Santiago, Chile

    Francesca Velarde

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  1. Francesca Velarde
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  2. Sarah Ezquerra
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  3. Xavier Delbruyere
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  6. Maroun Khoury
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FV, YH, and MK were involved in reading and editing the manuscript. All the authors drafted the manuscript and approved the final version.

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Correspondence to Yessia Hidalgo or Maroun Khoury.

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MK is the chief scientific officer of Cells for Cells and Regenero, the Chilean consortium for regenerative medicine. YH received a stipend from Regenero. AC is the chief executive officer of Dragon BioMed with spin-off of the Universidad San Francisco de Quito in regenerative medicine. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Velarde, F., Ezquerra, S., Delbruyere, X. et al. Mesenchymal stem cell-mediated transfer of mitochondria: mechanisms and functional impact. Cell. Mol. Life Sci. 79, 177 (2022). https://doi.org/10.1007/s00018-022-04207-3

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  • DOI: https://doi.org/10.1007/s00018-022-04207-3

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