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1.
Cell Transplant ; 32: 9636897221148457, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36624995

RESUMEN

Although mesenchymal stem cell transplantation has been successful in the treatment of ischemic cardiomyopathy, the underlying mechanisms remain unclear. Herein, we investigated whether mitochondrial transfer could explain the success of cell therapy in ischemic cardiomyopathy. Mitochondrial transfer in co-cultures of human adipose-derived mesenchymal stem cells and rat cardiomyocytes maintained under hypoxic conditions was examined. Functional recovery was monitored in a rat model of myocardial infarction following human adipose-derived mesenchymal stem cell transplantation. We observed mitochondrial transfer in vitro, which required the formation of cell-to-cell contacts and synergistically enhanced energy metabolism. Rat cardiomyocytes exhibited mitochondrial transfer 3 days following human adipose-derived mesenchymal stem cell transplantation to the ischemic heart surface post-myocardial infarction. We detected donor mitochondrial DNA in the recipient myocardium concomitant with a significant improvement in cardiac function. Mitochondrial transfer is vital for successful cell transplantation therapies and improves treatment outcomes in ischemic cardiomyopathy.


Asunto(s)
Cardiomiopatías , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Infarto del Miocardio , Ratas , Humanos , Animales , Miocardio/metabolismo , Infarto del Miocardio/terapia , Infarto del Miocardio/genética , Miocitos Cardíacos/metabolismo , Cardiomiopatías/terapia , Trasplante de Células Madre
2.
Regen Ther ; 18: 182-190, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34307796

RESUMEN

INTRODUCTION: Idiopathic dilated cardiomyopathy (DCM) is associated with abnormalities in cytoskeletal proteins, mitochondrial ATP transporter, microvasculature, and fibrosis. Mesenchymal stem cells (MSCs) can ameliorate distressed mitochondrial and structural proteins, as well as fibrosis, via the paracrine effect of cytokines. This study aimed to investigate whether the transplantation of adipose tissue-derived MSCs (ADSCs) reverses histological and functional abnormalities in the distressed myocardium of DCM-like hamsters by modulating the expression of adenine nucleotide translocase 1 (ANT-1). METHODS: Eighteen weeks after birth, ADSCs were implanted onto the cardiac surface of δ-sarcoglycan (SG)-deficient hamsters or sham surgery was performed. RESULTS: Left ventricular ejection fraction and end-systolic diameter were maintained in ADSC-treated animals for four weeks, ATP concentration was considerably elevated in the cardiomyocytes of these animals, and ANT-1 expression was significantly upregulated as well. The expression of extracellular matrix and myocardial cytoskeletal proteins, such as collagen, SG, and α-dystroglycan, did not differ between groups. However, significant improvements in myosin and Smad4 expression, cardiomyocyte hypertrophy, and capillary density occurred in the ADSC-treated group. CONCLUSIONS: We demonstrated that ADSCs might maintain cardiac function in the DCM hamster model by enhancing ATP concentration, as well as mitochondrial transporter and myosin expression, indicating their potential for DCM treatment.

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