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Updated: Apr 17, 2026
Ultrasound-Guided Induced Pluripotent Stem Cell-Derived Cardiomyocyte Implantation in Myocardial Infarcted Mice
Published on: March 30, 2022
MicroRNA-133a engineered mesenchymal stem cells augment cardiac function and cell survival in the infarct heart
Duaa Dakhlallah1, Jianying Zhang, Lianbo Yu
1*Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH; †Department of Engineering, American University of the Safat, Kuwait; ‡Department of Biomedical Informatics, Center for Biostatistics, The Ohio State University, Columbus, OH; and §Department of Emergency Medicine, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH.
Insights
Enhancing mesenchymal stem cells (MSCs) with miR-133a mimics improves their survival and cardiac function after myocardial infarction (MI). This bioengineering approach offers a promising strategy for stem cell therapy in treating heart damage.
Area of Science:
- Cardiovascular Research
- Regenerative Medicine
- Molecular Biology
Background:
- Cardiovascular disease, particularly myocardial infarction (MI), is a leading cause of mortality, often leading to heart failure.
- Mesenchymal stem cells (MSCs) show potential for cardiomyoplasty but suffer poor survival in infarcted hearts.
- miR-133a, a cardiac muscle microRNA, is downregulated in MI patients, suggesting a role in cardiac repair.
Purpose of the Study:
- To investigate if reprogramming MSCs with miR-133a mimics can enhance stem cell survival and therapeutic efficacy in an MI model.
- To evaluate the impact of miR-133a mimic-modified MSCs on cardiac function, fibrosis, and apoptosis post-MI.
Main Methods:
- MSCs were transfected with miR-133a mimics or antagomirs.
- miR-133a levels were quantified using real-time PCR.
- Transfected MSCs were implanted into rat hearts subjected to MI; cardiac function, fibrosis, and apoptosis-related gene expression were assessed.
Main Results:
- miR-133a mimic transfection improved MSC survival in vitro (MTT assay).
- Transplantation of miR-133a mimic-modified MSCs significantly increased cell engraftment, improved cardiac function, and reduced fibrosis in MI hearts.
- Pro-apoptotic gene expression (Apaf-1, Caspase-9, Caspase-3) was significantly decreased, with miR-133a confirmed as a direct target of Apaf-1.
Conclusions:
- Bioengineering MSCs with miR-133a mimics enhances their survival and promotes cardiac repair after MI.
- This miRNA-mediated stem cell modification strategy holds potential for improving outcomes in stem cell transplantation for myocardial infarction.
Abstract:
: Cardiovascular disease is the number 1 cause of morbidity and mortality in the United States. The most common manifestation of cardiovascular disease is myocardial infarction (MI), which can ultimately lead to congestive heart failure. Cell therapy (cardiomyoplasty) is a new potential therapeutic treatment alternative for the damaged heart. Recent preclinical and clinical studies have shown that mesenchymal stem cells (MSCs) are a promising cell type for cardiomyoplasty applications. However, a major limitation is the poor survival rate of transplanted stem cells in the infarcted heart. miR-133a is an abundantly expressed microRNA (miRNA) in the cardiac muscle and is downregulated in patients with MI. We hypothesized that reprogramming MSCs using miRNA mimics (double-stranded oligonucleotides) will improve survival of stem cells in the damaged heart. MSCs were transfected with miR-133a mimic and antagomirs, and the levels of miR-133a were measured by quantitative real-time polymerase chain reaction. Rat hearts were subjected to MI and MSCs transfected with miR-133a mimic or antagomir were implanted in the ischemic hearts. Four weeks after MI, cardiac function, cardiac fibrosis, miR-133a levels, and apoptosis-related genes (Apaf-1, Caspase-9, and Caspase-3) were measured in the heart. We found that transfecting MSCs with miR-133a mimic improves survival of MSCs as determined by the MTT assay. Similarly, transplantation of miR-133a mimic transfected MSCs in rat hearts subjected to MI led to a significant increase in cell engraftment, cardiac function, and decreased fibrosis when compared with MSCs only or MI groups. At the molecular level, quantitative real-time polymerase chain reaction data demonstrated a significant decrease in expression of the proapoptotic genes; Apaf-1, caspase-9, and caspase-3 in the miR-133a mimic transplanted group. Furthermore, luciferase reporter assay confirmed that miR-133a is a direct target for Apaf-1. Overall, bioengineering of stem cells through miRNAs manipulation could potentially improve the therapeutic outcome of patients undergoing stem cell transplantation for MI.
