Transfer of Cardiac Mitochondria Improves the Therapeutic Efficacy of Mesenchymal Stem Cells in a Preclinical Model of Ischemic Heart Disease.
cell therapy
mesenchymal stem cells
metabolism
mitochondria transfer
post-ischemic heart failure
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
11 02 2023
11 02 2023
Historique:
received:
16
12
2022
revised:
31
01
2023
accepted:
08
02
2023
entrez:
25
2
2023
pubmed:
26
2
2023
medline:
3
3
2023
Statut:
epublish
Résumé
The use of mesenchymal stem cells (MSCs) appears to be a promising therapeutic approach for cardiac repair after myocardial infarction. However, clinical trials have revealed the need to improve their therapeutic efficacy. Recent evidence demonstrated that mitochondria undergo spontaneous transfer from damaged cells to MSCs, resulting in the activation of the cytoprotective and pro-angiogenic functions of recipient MSCs. Based on these observations, we investigated whether the preconditioning of MSCs with mitochondria could optimize their therapeutic potential for ischemic heart disease. Human MSCs were exposed to mitochondria isolated from human fetal cardiomyocytes. After 24 h, the effects of mitochondria preconditioning on the MSCs' function were analyzed both in vitro and in vivo. We found that cardiac mitochondria-preconditioning improved the proliferation and repair properties of MSCs in vitro. Mechanistically, cardiac mitochondria mediate their stimulatory effects through the production of reactive oxygen species, which trigger their own degradation in recipient MSCs. These effects were further confirmed in vivo, as the mitochondria preconditioning of MSCs potentiated their therapeutic efficacy on cardiac function following their engraftment into infarcted mouse hearts. The preconditioning of MSCs with the artificial transfer of cardiac mitochondria appears to be promising strategy to improve the efficacy of MSC-based cell therapy in ischemic heart disease.
Sections du résumé
BACKGROUND
The use of mesenchymal stem cells (MSCs) appears to be a promising therapeutic approach for cardiac repair after myocardial infarction. However, clinical trials have revealed the need to improve their therapeutic efficacy. Recent evidence demonstrated that mitochondria undergo spontaneous transfer from damaged cells to MSCs, resulting in the activation of the cytoprotective and pro-angiogenic functions of recipient MSCs. Based on these observations, we investigated whether the preconditioning of MSCs with mitochondria could optimize their therapeutic potential for ischemic heart disease.
METHODS
Human MSCs were exposed to mitochondria isolated from human fetal cardiomyocytes. After 24 h, the effects of mitochondria preconditioning on the MSCs' function were analyzed both in vitro and in vivo.
RESULTS
We found that cardiac mitochondria-preconditioning improved the proliferation and repair properties of MSCs in vitro. Mechanistically, cardiac mitochondria mediate their stimulatory effects through the production of reactive oxygen species, which trigger their own degradation in recipient MSCs. These effects were further confirmed in vivo, as the mitochondria preconditioning of MSCs potentiated their therapeutic efficacy on cardiac function following their engraftment into infarcted mouse hearts.
CONCLUSIONS
The preconditioning of MSCs with the artificial transfer of cardiac mitochondria appears to be promising strategy to improve the efficacy of MSC-based cell therapy in ischemic heart disease.
Identifiants
pubmed: 36831249
pii: cells12040582
doi: 10.3390/cells12040582
pmc: PMC9953768
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
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