4.7 Article

Transplantation of MITO cells, mitochondria activated cardiac progenitor cells, to the ischemic myocardium of mouse enhances the therapeutic effect

Journal

SCIENTIFIC REPORTS
Volume 12, Issue 1, Pages -

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41598-022-08583-5

Keywords

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Funding

  1. Ministry of Education, Culture, Sports, Science and Technology [17H02094, 20K21872]
  2. Japanese Government (MEXT), JST FOREST [JPMJFR203X]
  3. Noguchi Institute
  4. Takeda Science Foundation
  5. Mochida Memorial Foundation for Medical and Pharmaceutical Research
  6. Grants-in-Aid for Scientific Research [20K21872] Funding Source: KAKEN

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This study aimed to validate the therapeutic effect of cell transplantation by using mitochondria-activated stem cells (MITO cells) in a mouse model of myocardial ischemia-reperfusion. The results showed that MITO cells transplanted group had better therapeutic effects, including weight gain, cardiac function improvement, and inhibition of fibrosis, compared to the non-transplanted group and CPC group.
Given the potential for myocardial stem cell transplantation as a promising treatment for heart failure, numerous clinical trials have been conducted and its usefulness has been clearly confirmed. However, the low rate of engraftment of transplanted cells has become a clinical problem, and this needs to be improved in the case of transplanting cells to the heart. To address this issue, we report on attempts to prepare mitochondria-activated stem cells (MITO cells) for use in transplantation. MITO cells, which is cardiac progenitor cells (CPCs) activated by the mitochondrial delivery of resveratrol with an anti-oxidant and mitochondrial activation effects were successfully prepared using a mitochondrial targeting nanocarrier (MITO-Porter). The purpose of this study was to validate the therapeutic effect of cell transplantation by the MITO cells using a mouse model of myocardial ischemia-reperfusion. Mouse CPCs were used as transplanted cells. The transplantation of CPCs and MITO cells were conducted after myocardial ischemia-reperfusion, and the therapeutic effect was determined. The MITO cells transplanted group showed increase in postoperative weight gain, improve cardiac function and inhibition of fibrosis compared to the non-transplanted group and the CPC group. The transplantation of MITO cells to the ischemic myocardium showed a stronger transplantation effect compared to conventional CPC transplantation.

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