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Published on: March 30, 2022
Integrin α4 Positive Subpopulation in Adipose Derived Stem Cells Effectively Reduces Infarct Size through Enhanced
Zihui Yuan1,2, Juan Tan1,2,3, Jian Wang1,2
1Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Insights
Adipose-derived stem cells (ASCs) show limited efficacy for myocardial infarction. A specific subpopulation, integrin α4+ ASCs, demonstrated improved survival, homing, and therapeutic benefits in preclinical models.
Area of Science:
- Regenerative Medicine
- Cardiovascular Research
- Stem Cell Biology
Background:
- Adipose-derived stem cells (ASCs) show promise for myocardial infarction (MI) treatment, but their therapeutic efficacy is hindered by poor survival and engraftment.
- Integrin-mediated cell adhesion is crucial for stem cell survival and homing, yet ASCs express insufficient integrin α4, limiting their potential in MI.
- Targeting specific integrin subpopulations may enhance ASC function and therapeutic outcomes in cardiovascular diseases.
Purpose of the Study:
- To characterize the integrin α4-positive (α4+) ASC subpopulation.
- To investigate the therapeutic efficacy of integrin α4+ ASCs in a preclinical model of myocardial infarction.
- To elucidate the mechanisms underlying the enhanced therapeutic potential of integrin α4+ ASCs.
Main Methods:
- Fluorescence-activated cell sorting was employed to isolate the integrin α4+ ASC subpopulation.
- In vitro characterization included assessments of angiogenic factor secretion, migration, and anti-apoptotic capacity.
- Positron emission tomography and cardiac cine MRI were utilized to evaluate infarct size and cardiac function in a myocardial infarction model.
Main Results:
- Integrin α4+ ASCs exhibited enhanced secretion of angiogenic growth factors, increased migration, and superior anti-apoptotic properties compared to unfractionated ASCs.
- Vascular cell adhesion molecule-1 (VCAM-1) upregulation post-MI facilitated interaction with integrin α4 on ASCs, improving survival and adhesion.
- Transplantation of integrin α4+ ASCs resulted in more robust engraftment, reduced infarct size, and improved cardiac function recovery in the MI model.
Conclusions:
- The integrin α4+ ASC subpopulation demonstrates superior therapeutic potential for ameliorating ischemic myocardial damage compared to unfractionated ASCs.
- Enhanced engraftment, migratory capacity, and paracrine factor release contribute to the improved efficacy of integrin α4+ ASCs in tissue repair.
- Targeting integrin α4 represents a promising strategy to enhance the therapeutic application of ASCs in myocardial infarction treatment.
Abstract:
The efficacy of adipose-derived stem cells (ASCs) on myocardial infarction is limited due to poor survival and engraftment. Integrin-mediated cell adhesion is a prerequisite for its survival and homing. ASCs expressed insufficient integrin α4, limiting their homing capacity. This study aims to characterize integrin α4＋ ASC subpopulation and investigate their therapeutic efficacy in myocardial infarction. We used fluorescence-activated cell sorting to harvest integrin α4＋ ASCs subpopulation, which were characterized in vitro and transplanted into myocardial infarction model. Positron emission tomography imaging were performed to measure infarction size. Cardiac cine magnetic resonance imaging was used to evaluate heart contractile function. Compared with the unfractionated ASCs, integrin α4＋ ASCs subpopulation secreted a higher level of angiogenic growth factors, migrated more rapidly, and exhibited a stronger anti-apoptotic capacity. Vascular cell adhesion molecule-1 was obviously up-regulated at 3 days after myocardial infarction, which interacted with integrin α4 receptor on the surface of ASCs to enhance the survival and adhesion. Thus, we implanted unfractionated ASCs or integrin α4＋ ASCs subpopulation into the 3-day infarcted myocardium. Integrin α4＋ ASCs subpopulation exhibited more robust engraftment into the infarcted myocardium. Integrin α4＋ ASCs subpopulation more effectively decreased infarct size and strengthen cardiac function recovery than did the unfractionated ASCs. Integrin α4＋ ASCs subpopulation is superior to unfractionated ASCs in ameliorating ischemic myocardial damage in animal model. Mechanistically, their more robust engraftment into the infarct area, higher migratory capacity and their increased release of paracrine factors contribute to enhanced tissue repair.
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