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Rutin and quercetagetin enhance the regeneration potential of young and aging bone marrow-derived mesenchymal stem cells in the rat infarcted myocardium

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Abstract

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 H2O2 which resulted in an increase in the ROS level. MSCs were treated with rutin or quercetagetin at varying concentrations and exposed to H2O2. It was observed that both antioxidants significantly (P < 0.001) suppressed H2O2-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.

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Authors and Affiliations

  1. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan

    Tuba Mustafa, Irfan Khan, Hana’a Iqbal, Sehrish Usman & Asmat Salim

  2. Dow Research Institute of Biotechnology and Biomedical Sciences (DRIBBS), Dow University of Health Sciences, Gulzar-E-Hijri, Suparco Road, KDA Scheme-33, Karachi, Pakistan

    Nadia Naeem

  3. H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan

    Shaheen Faizi

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  1. Tuba Mustafa
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  2. Irfan Khan
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Contributions

Each author contributed significantly and meets the criteria for authorship and assumes the corresponding responsibility. TM conducted all the experiments and wrote the first draft, with technical and analytical assistance from IK in the in vivo work, HI assisted in in vitro studies. Both IK and HI contributed in manuscript writing. SU conducted some of the experiments. NN assisted in the in vivo work, especially echocardiography. SF provided the expertise related to the chemical compounds. AS conceived the idea, critically analyzed the results and finalized the manuscript. All authors are in agreement with the content of the manuscript and reviewed the manuscript.

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Correspondence to Asmat Salim.

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Mustafa, T., Khan, I., Iqbal, H. et al. Rutin and quercetagetin enhance the regeneration potential of young and aging bone marrow-derived mesenchymal stem cells in the rat infarcted myocardium. Mol Cell Biochem 478, 1759–1770 (2023). https://doi.org/10.1007/s11010-022-04628-5

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