Role of miRNA-324-5p-Modified Adipose-Derived Stem Cells in Post-Myocardial Infarction Repair

Int J Stem Cells. 2021 Aug 30;14(3):298-309. doi: 10.15283/ijsc21025.

Abstract

Background and objectives: To seek out the role of mircoRNA (miR)-324-5p-modified adipose-derived stem cells (ADSCs) in post-myocardial infarction (MI) myocardial repair.

Methods and results: Rat ADSCs were cultivated and then identified by morphologic observation, osteogenesis and adipogenesis induction assays and flow cytometry. Afterwards, ADSCs were modified by miR-324-5p lentiviral vector, with ADSC proliferation and migration measured. Then, rat MI model was established, which was treated by ADSCs or miR-324-5p-modified ADSCs. Subsequently, the function of miR-324-5p-modified ADSCs in myocardial repair of MI rats was assessed through functional assays. Next, the binding relation of miR-324-5p and Toll-interacting protein (TOLLIP) was validated. Eventually, functional rescue assay of TOLLIP was performed to verify the role of TOLLIP in MI. First, rat ADSCs were harvested. Overexpressed miR-324-5p improved ADSC viability. ADSC transplantation moderately enhanced cardiac function of MI rats, reduced enzyme levels and decreased infarct size and apoptosis; while miR-324-5p-modified ADSCs could better promote post-MI repair. Mechanically, miR-324-5p targeted TOLLIP in myocardial tissues. Moreover, TOLLIP overexpression debilitated the promotive role of miR-324-5p-modified ADSCs in post-MI repair in rats.

Conclusions: miR-324-5p-modified ADSCs evidently strengthened post-MI myocardial repair by targeting TOLLIP in myocardial tissues.

Keywords: Adipose-derived stem cells; Myocardial infarction; Myocardial repair; Radiotherapy; Stem cell survival; mircoRNA-324-5p.