The therapeutic efficacy comparison of MSCs derived different tissues unveilings anti-apoptosis more crucial than angiogenesis in treating acute myocardial infarction
Abstract Background Myocardial infarction (MI) is a severe disease that often associated with impaired angiogenesis and increased myocardial apoptosis. Mesenchymal stromal cells (MSCs) have been a promising candidate for treating myocardial infarction. However, functional heterogeneity of MSCs leads...
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BMC
2025-05-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-025-04378-3 |
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| author | Mingjie Pan Yueyue Xu Yaping Wang Yue Jiang Yuanyuan Xie Chenxu Tai Wenqing Wang Bin Wang |
| author_facet | Mingjie Pan Yueyue Xu Yaping Wang Yue Jiang Yuanyuan Xie Chenxu Tai Wenqing Wang Bin Wang |
| author_sort | Mingjie Pan |
| collection | DOAJ |
| description | Abstract Background Myocardial infarction (MI) is a severe disease that often associated with impaired angiogenesis and increased myocardial apoptosis. Mesenchymal stromal cells (MSCs) have been a promising candidate for treating myocardial infarction. However, functional heterogeneity of MSCs leads to inconsistent therapeutic efficiency and the current MSCs-based therapy lacks the concept and implementation of precision medicine. In this study, we compared the cardioprotective effect of UCMSCs and ADMSCs targeting the angiogenesis in a mouse MI model and screened out optimum MSCs candidate for precise clinical application. Methods The gene expression profiles of UCMSCs and ADMSCs were investigated through RNA sequencing analysis. To compare their angiogenic potential, we performed tube formation assay, Matrigel plug assays, and aortic ring assay, and analyzed pro-angiogenic genes via qPCR. Subsequently, UCMSCs and ADMSCs were respectively injected into myocardium after MI surgery in mice. On day 28 post-MI, echocardiography was performed to assess cardiac function. Histological analysis was performed to assess MSCs retention, angiogenesis, and myocardial apoptosis. Additionally, the anti-apoptosis effects mediated by MSCs were further evaluated using flow cytometry in hypoxia H9C2 and HL-1 cells. Results The RNA sequencing analysis revealed differences in gene expression related to angiogenesis and apoptosis pathways between UCMSCs and ADMSCs. UCMSCs presented greater pro-angiogenesis activity than ADMSCs in vitro and in vivo. Both of UCMSCs and ADMSCs improved cardiac function, decreased infarction area and inhibited cardiomyocyte apoptosis while promoting angiogenesis post-MI in mice. Notably, ADMSCs exerted a better cardioprotective function than UCMSCs and stronger anti-apoptotic effect on residual cardiomyocytes. Conclusions The protection of residual cells survival played a more prominent role than angiogenesis in MSCs-based therapy for acute MI. Our study provides new insights into therapeutic strategies and suggests that the optimal type of MSCs can be screened based on their tissue heterogeneity for precise clinical applications in acute MI. |
| format | Article |
| id | doaj-art-9a05eb2d2105410883b563d9cc115d98 |
| institution | Kabale University |
| issn | 1757-6512 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj-art-9a05eb2d2105410883b563d9cc115d982025-08-20T03:53:57ZengBMCStem Cell Research & Therapy1757-65122025-05-0116111510.1186/s13287-025-04378-3The therapeutic efficacy comparison of MSCs derived different tissues unveilings anti-apoptosis more crucial than angiogenesis in treating acute myocardial infarctionMingjie Pan0Yueyue Xu1Yaping Wang2Yue Jiang3Yuanyuan Xie4Chenxu Tai5Wenqing Wang6Bin Wang7Clinical Medicine Research Center, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical SchoolThe Department of Thoracic and Cardiovascular Surgery, Nanjing First Hospital, Nanjing Medical UniversityClinical Stem Cell Center, Nanjing Drum Tower Hospital, Clinical Medical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese MedicineClinical Stem Cell Center, the Affiliated Drum Tower Hospital of Nanjing University Medical SchoolClinical Stem Cell Center, the Affiliated Drum Tower Hospital of Nanjing University Medical SchoolClinical Stem Cell Center, the Affiliated Drum Tower Hospital of Nanjing University Medical SchoolClinical Stem Cell Center, the Affiliated Drum Tower Hospital of Nanjing University Medical SchoolClinical Stem Cell Center, Nanjing Drum Tower Hospital, Clinical Medical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese MedicineAbstract Background Myocardial infarction (MI) is a severe disease that often associated with impaired angiogenesis and increased myocardial apoptosis. Mesenchymal stromal cells (MSCs) have been a promising candidate for treating myocardial infarction. However, functional heterogeneity of MSCs leads to inconsistent therapeutic efficiency and the current MSCs-based therapy lacks the concept and implementation of precision medicine. In this study, we compared the cardioprotective effect of UCMSCs and ADMSCs targeting the angiogenesis in a mouse MI model and screened out optimum MSCs candidate for precise clinical application. Methods The gene expression profiles of UCMSCs and ADMSCs were investigated through RNA sequencing analysis. To compare their angiogenic potential, we performed tube formation assay, Matrigel plug assays, and aortic ring assay, and analyzed pro-angiogenic genes via qPCR. Subsequently, UCMSCs and ADMSCs were respectively injected into myocardium after MI surgery in mice. On day 28 post-MI, echocardiography was performed to assess cardiac function. Histological analysis was performed to assess MSCs retention, angiogenesis, and myocardial apoptosis. Additionally, the anti-apoptosis effects mediated by MSCs were further evaluated using flow cytometry in hypoxia H9C2 and HL-1 cells. Results The RNA sequencing analysis revealed differences in gene expression related to angiogenesis and apoptosis pathways between UCMSCs and ADMSCs. UCMSCs presented greater pro-angiogenesis activity than ADMSCs in vitro and in vivo. Both of UCMSCs and ADMSCs improved cardiac function, decreased infarction area and inhibited cardiomyocyte apoptosis while promoting angiogenesis post-MI in mice. Notably, ADMSCs exerted a better cardioprotective function than UCMSCs and stronger anti-apoptotic effect on residual cardiomyocytes. Conclusions The protection of residual cells survival played a more prominent role than angiogenesis in MSCs-based therapy for acute MI. Our study provides new insights into therapeutic strategies and suggests that the optimal type of MSCs can be screened based on their tissue heterogeneity for precise clinical applications in acute MI.https://doi.org/10.1186/s13287-025-04378-3Myocardial infarctionMSCsHeterogeneityAngiogenesisApoptosis |
| spellingShingle | Mingjie Pan Yueyue Xu Yaping Wang Yue Jiang Yuanyuan Xie Chenxu Tai Wenqing Wang Bin Wang The therapeutic efficacy comparison of MSCs derived different tissues unveilings anti-apoptosis more crucial than angiogenesis in treating acute myocardial infarction Stem Cell Research & Therapy Myocardial infarction MSCs Heterogeneity Angiogenesis Apoptosis |
| title | The therapeutic efficacy comparison of MSCs derived different tissues unveilings anti-apoptosis more crucial than angiogenesis in treating acute myocardial infarction |
| title_full | The therapeutic efficacy comparison of MSCs derived different tissues unveilings anti-apoptosis more crucial than angiogenesis in treating acute myocardial infarction |
| title_fullStr | The therapeutic efficacy comparison of MSCs derived different tissues unveilings anti-apoptosis more crucial than angiogenesis in treating acute myocardial infarction |
| title_full_unstemmed | The therapeutic efficacy comparison of MSCs derived different tissues unveilings anti-apoptosis more crucial than angiogenesis in treating acute myocardial infarction |
| title_short | The therapeutic efficacy comparison of MSCs derived different tissues unveilings anti-apoptosis more crucial than angiogenesis in treating acute myocardial infarction |
| title_sort | therapeutic efficacy comparison of mscs derived different tissues unveilings anti apoptosis more crucial than angiogenesis in treating acute myocardial infarction |
| topic | Myocardial infarction MSCs Heterogeneity Angiogenesis Apoptosis |
| url | https://doi.org/10.1186/s13287-025-04378-3 |
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