International Journal of Stem Cells

Korean Society for Stem Cell Research (한국줄기세포학회)
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Integrin 𝛼4 Positive Subpopulation in Adipose Derived Stem Cells Effectively Reduces Infarct Size through Enhanced Engraftment into Myocardial Infarction

  • Zihui Yuan (Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology) ;
  • Juan Tan (Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology) ;
  • Jian Wang (Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology)
  • Received : 2022.12.21
  • Accepted : 2023.08.14
  • Published : 2024.02.28
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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.

Keywords

Acknowledgement

We would like to acknowledge the funding support provided by the National Natural Science Foundation of China (81770277, 82370469), the Natural Science Foundation of Hubei Province of China (2022CFB075), the Key Laboratory of Biological Targeted Therapy of Hubei Province (2021swbx020), and the Science Foundation of Wuhan Union Hospital (2021xhyn109).

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