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Therapeutic Effects of Mesenchymal Stromal Cells Require Mitochondrial Transfer and Quality Control
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 im...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10647450/ https://www.ncbi.nlm.nih.gov/pubmed/37958771 http://dx.doi.org/10.3390/ijms242115788 |
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author | Mukkala, Avinash Naraiah Jerkic, Mirjana Khan, Zahra Szaszi, Katalin Kapus, Andras Rotstein, Ori |
author_facet | Mukkala, Avinash Naraiah Jerkic, Mirjana Khan, Zahra Szaszi, Katalin Kapus, Andras Rotstein, Ori |
author_sort | Mukkala, Avinash Naraiah |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10647450 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-106474502023-10-31 Therapeutic Effects of Mesenchymal Stromal Cells Require Mitochondrial Transfer and Quality Control Mukkala, Avinash Naraiah Jerkic, Mirjana Khan, Zahra Szaszi, Katalin Kapus, Andras Rotstein, Ori Int J Mol Sci Review 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. MDPI 2023-10-31 /pmc/articles/PMC10647450/ /pubmed/37958771 http://dx.doi.org/10.3390/ijms242115788 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Mukkala, Avinash Naraiah Jerkic, Mirjana Khan, Zahra Szaszi, Katalin Kapus, Andras Rotstein, Ori Therapeutic Effects of Mesenchymal Stromal Cells Require Mitochondrial Transfer and Quality Control |
title | Therapeutic Effects of Mesenchymal Stromal Cells Require Mitochondrial Transfer and Quality Control |
title_full | Therapeutic Effects of Mesenchymal Stromal Cells Require Mitochondrial Transfer and Quality Control |
title_fullStr | Therapeutic Effects of Mesenchymal Stromal Cells Require Mitochondrial Transfer and Quality Control |
title_full_unstemmed | Therapeutic Effects of Mesenchymal Stromal Cells Require Mitochondrial Transfer and Quality Control |
title_short | Therapeutic Effects of Mesenchymal Stromal Cells Require Mitochondrial Transfer and Quality Control |
title_sort | therapeutic effects of mesenchymal stromal cells require mitochondrial transfer and quality control |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10647450/ https://www.ncbi.nlm.nih.gov/pubmed/37958771 http://dx.doi.org/10.3390/ijms242115788 |
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