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Journal Article Review Epublish 18 citations

PubMed: 37958771 DOI: 10.3390/ijms242115788

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

Int J Mol Sci 24(21)

Authors: Avinash Naraiah Mukkala, Mirjana Jerkic, Zahra Khan, Katalin Szaszi, Andras Kapus, Ori Rotstein

Affiliations

  • Unity Health Toronto, The Keenan Research Centre for Biomedical Science of St. Michael's Hospital, University of Toronto, Toronto, ON M5B 1T8, Canada.
  • Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada.
  • Unity Health Toronto, The Keenan Research Centre for Biomedical Science of St. Michael's Hospital, University of Toronto, Toronto, ON M5B 1T8, Canada. Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada.
  • Department of Surgery, University of Toronto, Toronto, ON M5T 1P5, Canada.

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.

MeSH

Mitochondria, Quality Control, Therapeutics, Ppar Gamma, Tissues, Peroxisome Proliferator-Activated Receptors, Stromal Cells, Organelle Biogenesis, Mesenchymal Stem Cells, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-Alpha

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