Transplantation of CRISPRa system engineered IL10-overexpressing bone marrow-derived mesenchymal stem cells for the treatment of myocardial infarction in diabetic mice
Abstract Background Myocardial infarction (MI) is a common cause of mortality in people. Mesenchymal stem cell (MSC) has been shown to exert therapeutic potential to treat myocardial infarction (MI). However, in patients with diabetes, the diabetic environment affected MSCs activity and could impair...
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| Format: | Article |
| Language: | English |
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BMC
2019-05-01
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| Series: | Journal of Biological Engineering |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13036-019-0163-6 |
| _version_ | 1828409203188826112 |
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| author | Xin Meng Minjuan Zheng Ming Yu Wei Bai Lei Zuo Xin Bu Yi Liu Linying Xia Jing Hu Liwen Liu Jianping Li |
| author_facet | Xin Meng Minjuan Zheng Ming Yu Wei Bai Lei Zuo Xin Bu Yi Liu Linying Xia Jing Hu Liwen Liu Jianping Li |
| author_sort | Xin Meng |
| collection | DOAJ |
| description | Abstract Background Myocardial infarction (MI) is a common cause of mortality in people. Mesenchymal stem cell (MSC) has been shown to exert therapeutic potential to treat myocardial infarction (MI). However, in patients with diabetes, the diabetic environment affected MSCs activity and could impair the efficacy of treatment. Interleukin-10 (IL-10) has been shown to attenuate MI by suppressing inflammation. In current study, the combination of MSC transplantation with IL-10 was evaluated in a diabetic mice model with MI. Methods We engineered bone marrow derived MSCs (BM-MSCs) to overexpress IL-10 by using CRISPR activation. We established the diabetic mice model with MI and monitored the IL-10 expression after BM-MSCs transplantation. We also evaluated the effects of BM-MSCs transplantation on inflammatory response, cell apoptosis, cardiac function and angiogenesis. Results CRISPR activation system enabled overexpression of IL-10 in BM-MSCs. Transplantation of BM-MSCs overexpressing IL-10 resulted in IL-10 expression in heart after transplantation. Transplantation of BM-MSCs overexpressing IL-10 inhibited inflammatory cell infiltration and pro-inflammatory cytokines production, improved cardiac functional recovery, alleviated cardiac injury, decreased apoptosis of cardiac cells and increased angiogenesis. Conclusion In summary, we have demonstrated the therapeutic potential of IL-10 overexpressed BM-MSCs in the treatment of MI in diabetic mice. |
| first_indexed | 2024-12-10T11:51:31Z |
| format | Article |
| id | doaj.art-34102568b6e14b0889587ba7ce4b1a65 |
| institution | Directory Open Access Journal |
| issn | 1754-1611 |
| language | English |
| last_indexed | 2024-12-10T11:51:31Z |
| publishDate | 2019-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Biological Engineering |
| spelling | doaj.art-34102568b6e14b0889587ba7ce4b1a652022-12-22T01:49:54ZengBMCJournal of Biological Engineering1754-16112019-05-0113111210.1186/s13036-019-0163-6Transplantation of CRISPRa system engineered IL10-overexpressing bone marrow-derived mesenchymal stem cells for the treatment of myocardial infarction in diabetic miceXin Meng0Minjuan Zheng1Ming Yu2Wei Bai3Lei Zuo4Xin Bu5Yi Liu6Linying Xia7Jing Hu8Liwen Liu9Jianping Li10Department of Ultrasonography, Xijing Hospital, the Fourth Military Medical UniversityDepartment of Ultrasonography, Xijing Hospital, the Fourth Military Medical UniversityDepartment of Ultrasonography, Xijing Hospital, the Fourth Military Medical UniversityDepartment of Ultrasonography, Xijing Hospital, the Fourth Military Medical UniversityDepartment of Ultrasonography, Xijing Hospital, the Fourth Military Medical UniversityDepartment of Biochemistry and Molecular Biology, the Fourth Military Medical UniversityDepartment of Cardiology, Xijing Hospital, the Fourth Military Medical UniversityDepartment of Cardiology, Xijing Hospital, the Fourth Military Medical UniversityDepartment of Radiation Oncology, Xijing Hospital, the Fourth Military Medical UniversityDepartment of Ultrasonography, Xijing Hospital, the Fourth Military Medical UniversityDepartment of Radiation Oncology, Xijing Hospital, the Fourth Military Medical UniversityAbstract Background Myocardial infarction (MI) is a common cause of mortality in people. Mesenchymal stem cell (MSC) has been shown to exert therapeutic potential to treat myocardial infarction (MI). However, in patients with diabetes, the diabetic environment affected MSCs activity and could impair the efficacy of treatment. Interleukin-10 (IL-10) has been shown to attenuate MI by suppressing inflammation. In current study, the combination of MSC transplantation with IL-10 was evaluated in a diabetic mice model with MI. Methods We engineered bone marrow derived MSCs (BM-MSCs) to overexpress IL-10 by using CRISPR activation. We established the diabetic mice model with MI and monitored the IL-10 expression after BM-MSCs transplantation. We also evaluated the effects of BM-MSCs transplantation on inflammatory response, cell apoptosis, cardiac function and angiogenesis. Results CRISPR activation system enabled overexpression of IL-10 in BM-MSCs. Transplantation of BM-MSCs overexpressing IL-10 resulted in IL-10 expression in heart after transplantation. Transplantation of BM-MSCs overexpressing IL-10 inhibited inflammatory cell infiltration and pro-inflammatory cytokines production, improved cardiac functional recovery, alleviated cardiac injury, decreased apoptosis of cardiac cells and increased angiogenesis. Conclusion In summary, we have demonstrated the therapeutic potential of IL-10 overexpressed BM-MSCs in the treatment of MI in diabetic mice.http://link.springer.com/article/10.1186/s13036-019-0163-6CRISPRaIL-10BM-MSCsMyocardial infarctionDiabete |
| spellingShingle | Xin Meng Minjuan Zheng Ming Yu Wei Bai Lei Zuo Xin Bu Yi Liu Linying Xia Jing Hu Liwen Liu Jianping Li Transplantation of CRISPRa system engineered IL10-overexpressing bone marrow-derived mesenchymal stem cells for the treatment of myocardial infarction in diabetic mice Journal of Biological Engineering CRISPRa IL-10 BM-MSCs Myocardial infarction Diabete |
| title | Transplantation of CRISPRa system engineered IL10-overexpressing bone marrow-derived mesenchymal stem cells for the treatment of myocardial infarction in diabetic mice |
| title_full | Transplantation of CRISPRa system engineered IL10-overexpressing bone marrow-derived mesenchymal stem cells for the treatment of myocardial infarction in diabetic mice |
| title_fullStr | Transplantation of CRISPRa system engineered IL10-overexpressing bone marrow-derived mesenchymal stem cells for the treatment of myocardial infarction in diabetic mice |
| title_full_unstemmed | Transplantation of CRISPRa system engineered IL10-overexpressing bone marrow-derived mesenchymal stem cells for the treatment of myocardial infarction in diabetic mice |
| title_short | Transplantation of CRISPRa system engineered IL10-overexpressing bone marrow-derived mesenchymal stem cells for the treatment of myocardial infarction in diabetic mice |
| title_sort | transplantation of crispra system engineered il10 overexpressing bone marrow derived mesenchymal stem cells for the treatment of myocardial infarction in diabetic mice |
| topic | CRISPRa IL-10 BM-MSCs Myocardial infarction Diabete |
| url | http://link.springer.com/article/10.1186/s13036-019-0163-6 |
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