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Published on: September 3, 2020
Priming mesenchymal stem cells boosts stem cell therapy to treat myocardial infarction
Juliana L Carvalho1, Vinicius B A Braga, Marcos B Melo
1Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil. julianalott@gmail.com
Insights
Priming mesenchymal stem cells (MSCs) to a heart-muscle-like state significantly improved their effectiveness in treating myocardial infarction in rats. This enhanced stem cell therapy offers a promising new avenue for cardiovascular disease treatment.
Area of Science:
- Cardiology
- Regenerative Medicine
- Stem Cell Biology
Background:
- Cardiovascular diseases represent a leading global cause of mortality.
- Current treatments for myocardial infarction have limited efficacy.
- Adult stem cell therapies show some benefits but require improvement for clinical application.
Purpose of the Study:
- To investigate if priming mesenchymal stem cells (MSCs) towards a cardiomyogenic lineage enhances their therapeutic effects in acute myocardial infarction.
- To assess the in vivo efficacy of primed MSCs (pMSCs) compared to undifferentiated MSCs in a rat model.
Main Methods:
- Mesenchymal stem cells were cultured in cardiomyogenic media for 4 days to induce priming.
- Primed and unprimed MSCs were characterized in vitro for cardiomyogenic gene and protein expression (Cx-43, sarcomeric α-actinin).
- Both cell types were administered to rats immediately following induced myocardial infarction (left anterior descending occlusion).
Main Results:
- Primed MSCs (pMSCs) demonstrated superior improvement in cardiac function compared to undifferentiated MSCs post-myocardial infarction.
- Both MSCs and pMSCs were detectable in the myocardium 7 days after transplantation.
- Higher expression of Connexin-43 was observed in pMSCs, potentially explaining their enhanced therapeutic performance.
Conclusions:
- Priming mesenchymal stem cells towards a cardiomyogenic lineage significantly enhances their therapeutic potential for acute myocardial infarction.
- The improved efficacy of pMSCs may be attributed to factors like enhanced Connexin-43 expression.
- This approach represents a promising strategy for improving stem cell-based therapies for cardiovascular diseases.
Abstract:
Cardiovascular diseases are the number one cause of death globally and are projected to remain the single leading cause of death. Treatment options abounds, although efficacy is limited. Recent studies attribute discrete and ephemeral benefits to adult stem cell therapies, indicating the urge to improve stem cell based-therapy. In this study, we show that priming mesenchymal stem cells (MSC) towards cardiomyogenic lineage enhances their beneficial effects in vivo as treatment option for acute phase myocardial infarction. MSC were primed using cardiomyogenic media for 4 days, after which peak expression of key cardiomyogenic genes are reached and protein expression of Cx-43 and sarcomeric α-actinin are observed. MSC and primed MSC (pMSC) were characterized in vitro and used to treat infarcted rats immediately after left anterior descending (LAD) occlusion. Echocardiography analysis indicated that MSC-treated myocardium presented discrete improvement in function, but it also showed that pMSC treatment lead to superior beneficial results, compared with undifferentiated MSC. Seven days after cell injection, MSC and pMSC could still be detected in the myocardium. Connexin-43 expression was quantified through immunoblotting, and was superior in pMSC, indicating that this could be a possible explanation for the superior performance of pMSC therapy.
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