Human MuStem Cell Grafting into Infarcted Rat Heart Attenuates Adverse Tissue Remodeling and Preserves Cardiac
Alice Rannou1,2,3, Gilles Toumaniantz2,3, Thibaut Larcher1
1PAnTher, INRA, École Nationale Vétérinaire, Agro-Alimentaire et de l'Alimentation Nantes-Atlantique (Oniris), Université Bretagne Loire (UBL), 44307 Nantes, France.
Insights
Human MuStem cells show potential for treating myocardial infarction by reducing fibrosis and improving heart function. These muscle-derived stem cells promote tissue repair and angiogenesis in infarcted hearts.
Area of Science:
- Regenerative Medicine
- Cardiovascular Research
- Stem Cell Biology
Background:
- Myocardial infarction (MI) is a major global health concern with limited effective treatments.
- Previous cell therapies for MI have shown insufficient structural and functional benefits in clinical settings.
- Muscle-derived stem cells (MuStem cells) have demonstrated efficacy in skeletal muscle repair, including enhanced survival and engraftment.
Purpose of the Study:
- To investigate the therapeutic potential of human MuStem cells for repairing infarcted hearts.
- To evaluate the effects of MuStem cell transplantation on cardiac structure and function post-myocardial infarction.
Main Methods:
- Human MuStem cells were administered locally to immunodeficient rats one week after induced myocardial infarction.
- Cardiac fibrosis, angiogenesis, left-ventricle dimensions, and contractile function were assessed three weeks post-transplantation.
- Histological analysis was performed to detect the presence and integration of human muscle fibers within the infarct zone.
Main Results:
- MuStem cell transplantation significantly reduced cardiac fibrosis and increased angiogenesis in the infarcted area.
- Foci of human muscle fibers were detected within the infarct site, indicating successful engraftment and differentiation.
- Treated rats exhibited attenuated left-ventricle dilation and preserved cardiac contractile function.
- No spontaneous arrhythmias were observed in the MuStem cell-treated group.
Conclusions:
- Human MuStem cells demonstrate significant potential for myocardial infarction repair, offering structural and functional benefits.
- MuStem cells promote angiogenesis, reduce fibrosis, and contribute to cardiac tissue regeneration post-MI.
- These findings position MuStem cells as a promising therapeutic candidate for muscle-regenerative medicine in cardiovascular disease.
Abstract:
Myocardial infarction is one of the leading causes of mortality and morbidity worldwide. Whereas transplantation of several cell types into the infarcted heart has produced promising preclinical results, clinical studies using analogous human cells have shown limited structural and functional benefits. In dogs and humans, we have described a type of muscle-derived stem cells termed MuStem cells that efficiently promoted repair of injured skeletal muscle. Enhanced survival rate, long-term engraftment, and participation in muscle fiber formation were reported, leading to persistent tissue remodeling and clinical benefits. With the consideration of these features that are restricted or absent in cells tested so far for myocardial infarction, we wanted to investigate the capacity of human MuStem cells to repair infarcted hearts. Their local administration in immunodeficient rats 1 week after induced infarction resulted in reduced fibrosis and increased angiogenesis 3 weeks post-transplantation. Importantly, foci of human fibers were detected in the infarct site. Treated rats also showed attenuated left-ventricle dilation and preservation of contractile function. Interestingly, no spontaneous arrhythmias were observed. Our findings support the potential of MuStem cells, which have already been proposed as therapeutic candidates for dystrophic patients, to treat myocardial infarction and position them as an attractive tool for muscle-regenerative medicine.
