Engineering a Human Pluripotent Stem Cell-Based in vitro Microphysiological System for Studying the Metformin Response in Aortic Smooth Muscle Cells
Aortic aneurysm is a common cardiovascular disease characterised by continuous dilation of the aorta, and this disease places a heavy burden on healthcare worldwide. Few drugs have been suggested to be effective in controlling the progression of aortic aneurysms. Preclinical drug responses from trad...
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Frontiers Media S.A.
2021-03-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2021.627877/full |
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| author | Nan Chen Nan Chen Mieradilijiang Abudupataer Mieradilijiang Abudupataer Sisi Feng Shichao Zhu Shichao Zhu Wenrui Ma Wenrui Ma Jun Li Jun Li Hao Lai Hao Lai Kai Zhu Kai Zhu Chunsheng Wang Chunsheng Wang |
| author_facet | Nan Chen Nan Chen Mieradilijiang Abudupataer Mieradilijiang Abudupataer Sisi Feng Shichao Zhu Shichao Zhu Wenrui Ma Wenrui Ma Jun Li Jun Li Hao Lai Hao Lai Kai Zhu Kai Zhu Chunsheng Wang Chunsheng Wang |
| author_sort | Nan Chen |
| collection | DOAJ |
| description | Aortic aneurysm is a common cardiovascular disease characterised by continuous dilation of the aorta, and this disease places a heavy burden on healthcare worldwide. Few drugs have been suggested to be effective in controlling the progression of aortic aneurysms. Preclinical drug responses from traditional cell culture and animals are usually controversial. An effective in vitro model is of great demand for successful drug screening. In this study, we induced an in vitro microphysiological system to test metformin, which is a potential drug for the treatment of aortic aneurysms. Human pluripotent stem cell-derived aortic smooth muscle cells (hPSC-HASMCs) were cultured on an in vitro microphysiological system, which could replicate the cyclic stretch of the human native aortic wall. By using this system, we found that HASMCs were more likely to present a physiologically contractile phenotype compared to static cell cultures. Moreover, we used hPSC-HASMCs in our microphysiological system to perform metformin drug screening. The results showed that hPSC-HASMCs presented a more contractile phenotype via NOTCH 1 signalling while being treated with metformin. This result indicated that metformin could be utilised to rescue hPSC-HASMCs from phenotype switching during aortic aneurysm progression. This study helps to elucidate potential drug targets for the treatment of aortic aneurysms. |
| first_indexed | 2024-12-17T08:39:28Z |
| format | Article |
| id | doaj.art-e9a7849dd648413fa56d9cb31ff78e80 |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-12-17T08:39:28Z |
| publishDate | 2021-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-e9a7849dd648413fa56d9cb31ff78e802022-12-21T21:56:23ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852021-03-01910.3389/fbioe.2021.627877627877Engineering a Human Pluripotent Stem Cell-Based in vitro Microphysiological System for Studying the Metformin Response in Aortic Smooth Muscle CellsNan Chen0Nan Chen1Mieradilijiang Abudupataer2Mieradilijiang Abudupataer3Sisi Feng4Shichao Zhu5Shichao Zhu6Wenrui Ma7Wenrui Ma8Jun Li9Jun Li10Hao Lai11Hao Lai12Kai Zhu13Kai Zhu14Chunsheng Wang15Chunsheng Wang16Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, ChinaShanghai Institute of Cardiovascular Diseases, Shanghai, ChinaDepartment of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, ChinaShanghai Institute of Cardiovascular Diseases, Shanghai, ChinaState Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, ChinaDepartment of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, ChinaShanghai Institute of Cardiovascular Diseases, Shanghai, ChinaDepartment of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, ChinaShanghai Institute of Cardiovascular Diseases, Shanghai, ChinaDepartment of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, ChinaShanghai Institute of Cardiovascular Diseases, Shanghai, ChinaDepartment of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, ChinaShanghai Institute of Cardiovascular Diseases, Shanghai, ChinaDepartment of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, ChinaShanghai Institute of Cardiovascular Diseases, Shanghai, ChinaDepartment of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, ChinaShanghai Institute of Cardiovascular Diseases, Shanghai, ChinaAortic aneurysm is a common cardiovascular disease characterised by continuous dilation of the aorta, and this disease places a heavy burden on healthcare worldwide. Few drugs have been suggested to be effective in controlling the progression of aortic aneurysms. Preclinical drug responses from traditional cell culture and animals are usually controversial. An effective in vitro model is of great demand for successful drug screening. In this study, we induced an in vitro microphysiological system to test metformin, which is a potential drug for the treatment of aortic aneurysms. Human pluripotent stem cell-derived aortic smooth muscle cells (hPSC-HASMCs) were cultured on an in vitro microphysiological system, which could replicate the cyclic stretch of the human native aortic wall. By using this system, we found that HASMCs were more likely to present a physiologically contractile phenotype compared to static cell cultures. Moreover, we used hPSC-HASMCs in our microphysiological system to perform metformin drug screening. The results showed that hPSC-HASMCs presented a more contractile phenotype via NOTCH 1 signalling while being treated with metformin. This result indicated that metformin could be utilised to rescue hPSC-HASMCs from phenotype switching during aortic aneurysm progression. This study helps to elucidate potential drug targets for the treatment of aortic aneurysms.https://www.frontiersin.org/articles/10.3389/fbioe.2021.627877/fullaortic aneurysmmetformindrug screeninghuman pluripotent stem cellsmicrophysiological system |
| spellingShingle | Nan Chen Nan Chen Mieradilijiang Abudupataer Mieradilijiang Abudupataer Sisi Feng Shichao Zhu Shichao Zhu Wenrui Ma Wenrui Ma Jun Li Jun Li Hao Lai Hao Lai Kai Zhu Kai Zhu Chunsheng Wang Chunsheng Wang Engineering a Human Pluripotent Stem Cell-Based in vitro Microphysiological System for Studying the Metformin Response in Aortic Smooth Muscle Cells Frontiers in Bioengineering and Biotechnology aortic aneurysm metformin drug screening human pluripotent stem cells microphysiological system |
| title | Engineering a Human Pluripotent Stem Cell-Based in vitro Microphysiological System for Studying the Metformin Response in Aortic Smooth Muscle Cells |
| title_full | Engineering a Human Pluripotent Stem Cell-Based in vitro Microphysiological System for Studying the Metformin Response in Aortic Smooth Muscle Cells |
| title_fullStr | Engineering a Human Pluripotent Stem Cell-Based in vitro Microphysiological System for Studying the Metformin Response in Aortic Smooth Muscle Cells |
| title_full_unstemmed | Engineering a Human Pluripotent Stem Cell-Based in vitro Microphysiological System for Studying the Metformin Response in Aortic Smooth Muscle Cells |
| title_short | Engineering a Human Pluripotent Stem Cell-Based in vitro Microphysiological System for Studying the Metformin Response in Aortic Smooth Muscle Cells |
| title_sort | engineering a human pluripotent stem cell based in vitro microphysiological system for studying the metformin response in aortic smooth muscle cells |
| topic | aortic aneurysm metformin drug screening human pluripotent stem cells microphysiological system |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2021.627877/full |
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