Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan.
Dow Research Institute of Biotechnology and Biomedical Sciences (DRIBBS), Dow University of Health Sciences, Gulzar-E-Hijri, Suparco Road, KDA Scheme-33, Karachi, Pakistan.
Mol Cell Biochem. 2023 Aug;478(8):1759-1770. doi: 10.1007/s11010-022-04628-5. Epub 2022 Dec 25.
Myocardial infarction (MI) damages cardiomyocytes permanently and compromises cardiac function. Mesenchymal stem cells (MSCs) with the potential to differentiate into multiple lineages are considered as one of the best options for the treatment of MI. However, aging affects their regeneration capability. With age, reactive oxygen species (ROS) accumulate in cells ultimately causing cell death. To successfully utilize these stem cells in clinic, novel strategies to improve their functional capability should be explored. In this study, we aimed to enhance the cardiac regeneration potential of bone marrow MSCs derived from aging rats by treating them with antioxidants, rutin or quercetagetin in separate in vivo experiments. Oxidative stress was induced by treating MSCs of young and aging rats with different concentrations of HO which resulted in an increase in the ROS level. MSCs were treated with rutin or quercetagetin at varying concentrations and exposed to HO. It was observed that both antioxidants significantly (P < 0.001) suppressed HO-induced intracellular ROS accumulation in a dose-dependent manner. An optimized concentration of 10 µM rutin or quercetagetin was used for the in vivo experiments. MI models were developed in aging rats by ligation of left anterior descending artery and treated MSCs were transplanted in the MI models. Echocardiography was performed after 2 and 4 weeks of cell transplantation to evaluate the functional status of the infarcted heart and histological analysis was performed after 4 weeks to assess cardiac regeneration. Significant improvement was observed in cardiac parameters including LVEF% (P < 0.001), LVFS% (P < 0.01 and P < 0.001), LVIDd (P < 0.01 and P < 0.001), LVIDs (P < 0.001), LVEDV (P < 0.001) and LVESV (P < 0.001) in the treated young as well as aging MSCs. It is concluded from these findings that rutin and quercetagetin treatment enhance the regeneration efficiency of young and aging MSCs in vivo. These antioxidants can be effectively utilized to improve cellular therapy for myocardial infarction by suppressing ROS production.
心肌梗死（MI）会永久性地损伤心肌细胞，从而损害心脏功能。间充质干细胞（MSCs）具有向多个谱系分化的潜力，被认为是治疗 MI 的最佳选择之一。然而，衰老会影响其再生能力。随着年龄的增长，细胞内的活性氧（ROS）会积聚，最终导致细胞死亡。为了在临床上成功地利用这些干细胞，应该探索新的策略来提高它们的功能能力。在这项研究中，我们旨在通过在体内实验中用抗氧化剂芦丁或槲皮素处理来自衰老大鼠的骨髓间充质干细胞，来增强其心脏再生潜力。用不同浓度的 HO 处理年轻和衰老大鼠的 MSCs 诱导氧化应激，导致 ROS 水平升高。用不同浓度的芦丁或槲皮素处理 MSCs，并暴露于 HO 中。结果表明，两种抗氧化剂均能显著（P<0.001）以剂量依赖的方式抑制 HO 诱导的细胞内 ROS 积累。使用 10 μM 芦丁或槲皮素的优化浓度进行体内实验。通过结扎左前降支在衰老大鼠中建立 MI 模型，并将处理后的 MSCs 移植到 MI 模型中。在细胞移植后 2 周和 4 周进行超声心动图检查，以评估梗死心脏的功能状态，并在 4 周后进行组织学分析，以评估心脏再生。观察到心脏参数有显著改善，包括 LVEF%（P<0.001）、LVFS%（P<0.01 和 P<0.001）、LVIDd（P<0.01 和 P<0.001）、LVIDs（P<0.001）、LVEDV（P<0.001）和 LVESV（P<0.001）在处理后的年轻和衰老 MSCs 中均有改善。这些发现表明，芦丁和槲皮素处理可增强年轻和衰老 MSCs 在体内的再生效率。这些抗氧化剂可有效地用于抑制 ROS 产生，从而改善心肌梗死的细胞治疗。
