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从培养在纳米纤维支架上的干细胞生成心肌细胞:心肌梗死后的实验方法。

Generation of cardiomyocytes from stem cells cultured on nanofibrous scaffold: Experimental approach for attenuation of myocardial infarction.

机构信息

Hormones Department, Medical Research and Clinical Studies Institute, National Research Centre, Giza, Egypt; Stem Cell Lab., Center of Excellence for Advanced Sciences, National Research Centre, Giza, Egypt.

Hormones Department, Medical Research and Clinical Studies Institute, National Research Centre, Giza, Egypt; Stem Cell Lab., Center of Excellence for Advanced Sciences, National Research Centre, Giza, Egypt.

出版信息

Tissue Cell. 2024 Aug;89:102461. doi: 10.1016/j.tice.2024.102461. Epub 2024 Jul 4.

Abstract

The current study was constructed to fabricate polyamide based nanofibrous scaffolds (NS) and to define the most promising one for the generation of cardiomyocytes from adipose tissue derived mesenchymal stem cells (ADMSCs). This purpose was extended to assess the potentiality of the generated cardiomyocytes in relieving myocardial infarction (MI) in rats. Production and characterization of NSs were carried out. ADMSCs were cultured on NS and induced to differentiate into cardiomyocytes by specific growth factors. Molecular analysis for myocyte-specific enhancer factor 2 C (MEF2C) and alpha sarcomeric actin (α-SCA) expression was done to confirm the differentiation of ADMSCs into cardiomyocytes for further transplantation into MI induced rats. Implantation of cells in MI afflicted rats boosted heart rate, ST height and PR interval and lessened P duration, RR, QTc and QRS intervals. Also, this type of medication minified serum lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) enzymes activity as well as serum and cardiac troponin T (Tn-T) levels and upraised serum and cardiac α-SCA and cardiac connexin 43 (CX 43) levels. Microscopic feature of cardiac tissue sections of rats in the treated groups revealed great renovation in the cardiac microarchitecture. Conclusively, this attempt gains insight into a realistic strategy for recovery of MI through systemic employment of in vitro generated cardiomyocytes.

摘要

本研究旨在构建基于聚酰胺的纳米纤维支架 (NS),并确定最有前途的支架用于从脂肪组织来源的间充质干细胞 (ADMSC) 生成心肌细胞。这项研究旨在评估所生成的心肌细胞在缓解大鼠心肌梗死 (MI) 中的潜力。进行了 NS 的制备和表征。将 ADMSC 培养在 NS 上,并通过特定的生长因子诱导其分化为心肌细胞。进行肌细胞特异性增强因子 2C (MEF2C) 和 α 横纹肌肌动蛋白 (α-SCA) 表达的分子分析,以确认 ADMSC 分化为心肌细胞,进一步移植到诱导 MI 的大鼠中。将细胞植入 MI 大鼠中可提高心率、ST 高度和 PR 间隔,缩短 P 持续时间、RR、QTc 和 QRS 间隔。此外,这种治疗方法可降低血清乳酸脱氢酶 (LDH) 和肌酸激酶-MB (CK-MB) 酶活性以及血清和心肌肌钙蛋白 T (Tn-T) 水平,并提高血清和心肌 α-SCA 和心肌连接蛋白 43 (CX 43) 水平。治疗组大鼠心脏组织切片的显微镜特征显示,心脏微结构得到了很大的修复。总之,这项尝试为通过系统应用体外生成的心肌细胞来恢复 MI 提供了一种切实可行的策略。

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