Escin Preincubation Enhances the Therapeutic Effect of Umbilical Cord-Derived Mesenchymal Stem Cells in a Rat Model of Myocardial Infarction

Introduction: Umbilical cord-derived mesenchymal stem cells (UCMSCs) are promising candidates for the treatment of myocardial infarction (MI). However, their low mobility and survival limit their clinical applicability. This study aimed to enhance the therapeutic potential of UCMSCs by preincubating them with escin, a natural medicine derived from the dried mature seeds of Aesculus wilsonii.

Methods: We characterized the functional properties of UCMSCs before and after escin preconditioning in vitro. Additionally, we performed RNA Sequencing (RNA-seq) to analyze the transcriptomic differences between untreated and escin-pretreated UCMSCs (E-UCMSCs), followed by Western blot (WB) validation of the differentially expressed genes. In vivo, an MI model was established in rats, which involved permanent ligation of the left anterior descending coronary artery, followed by intravenous administration of UCMSCs and E-UCMSCs through the tail vein. The therapeutic efficacy of UCMSCs and E-UCMSCs was assessed by cardiac function measurements and Masson's trichrome staining to quantify fibrosis.

Results: No significant differences were observed in the basic characteristics of the UCMSCs before and after escin pretreatment. RNA-seq results demonstrated higher expression of intercellular adhesion molecule 1 (ICAM1) and GATA-binding protein 4 (GATA4) in E-UCMSCs than in UCMSCs. Furthermore, WB results confirmed this phenomenon. Most importantly, E-UCMSCs significantly restored myocardial contractile function and reduced infarct size in MI rats.

Conclusions: The current study demonstrates that escin upregulated ICAM1 and GATA4 gene expression in UCMSCs, thereby enhancing the therapeutic efficacy of UCMSCs in rats with MI. Therefore, pretreatment of UCMSCs with escin is a promising approach for the treatment of MI.

cardiac function; escin; myocardial infarction; transcriptomics; umbilical cord-derived mesenchymal stem cells (UCMSCs).