Engineering hiPSC-CM and hiPSC-EC laden 3D nanofibrous splenic hydrogel for improving cardiac function through revascularization and remuscularization in infarcted heart
Cell therapy has been a promising strategy for cardiac repair after myocardial infarction (MI), but a poor ischemic environment and low cell delivery efficiency remain significant challenges. The spleen serves as a hematopoietic stem cell niche and secretes cardioprotective factors after MI, but it...
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2021-12-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X21001766 |
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| author | Ge Guan Da Huo Yanzhao Li Xiaolin Zhao Yinghao Li Zhongliang Qin Dayu Sun Guanyuan Yang Mingcan Yang Ju Tan Wen Zeng Chuhong Zhu |
| author_facet | Ge Guan Da Huo Yanzhao Li Xiaolin Zhao Yinghao Li Zhongliang Qin Dayu Sun Guanyuan Yang Mingcan Yang Ju Tan Wen Zeng Chuhong Zhu |
| author_sort | Ge Guan |
| collection | DOAJ |
| description | Cell therapy has been a promising strategy for cardiac repair after myocardial infarction (MI), but a poor ischemic environment and low cell delivery efficiency remain significant challenges. The spleen serves as a hematopoietic stem cell niche and secretes cardioprotective factors after MI, but it is unclear whether it could be used for human pluripotent stem cell (hiPSC) cultivation and provide a proper microenvironment for cell grafts against the ischemic environment. Herein, we developed a splenic extracellular matrix derived thermoresponsive hydrogel (SpGel). Proteomics analysis indicated that SpGel is enriched with proteins known to modulate the Wnt signaling pathway, cell-substrate adhesion, cardiac muscle contraction and oxidation-reduction processes. In vitro studies demonstrated that hiPSCs could be efficiently induced into endothelial cells (iECs) and cardiomyocytes (iCMs) with enhanced function on SpGel. The cytoprotective effect of SpGel on iECs/iCMs against oxidative stress damage was also proven. Furthermore, in vivo studies revealed that iEC/iCM-laden SpGel improved cardiac function and inhibited cardiac fibrosis of infarcted hearts by improving cell survival, revascularization and remuscularization. In conclusion, we successfully established a novel platform for the efficient generation and delivery of autologous cell grafts, which could be a promising clinical therapeutic strategy for cardiac repair and regeneration after MI. |
| first_indexed | 2024-04-24T08:23:58Z |
| format | Article |
| id | doaj.art-b0c661d669184383b32a1635bd5b8b46 |
| institution | Directory Open Access Journal |
| issn | 2452-199X |
| language | English |
| last_indexed | 2024-04-24T08:23:58Z |
| publishDate | 2021-12-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj.art-b0c661d669184383b32a1635bd5b8b462024-04-16T23:54:11ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2021-12-0161244154429Engineering hiPSC-CM and hiPSC-EC laden 3D nanofibrous splenic hydrogel for improving cardiac function through revascularization and remuscularization in infarcted heartGe Guan0Da Huo1Yanzhao Li2Xiaolin Zhao3Yinghao Li4Zhongliang Qin5Dayu Sun6Guanyuan Yang7Mingcan Yang8Ju Tan9Wen Zeng10Chuhong Zhu11Department of Anatomy, State Key Laboratory of Trauma, Burn and Combined Injury, Key Lab for Biomechanics and Tissue Engineering of Chongqing, Army Medical University (Third Military Medical University), Chongqing, 400038, ChinaDepartment of Anatomy, State Key Laboratory of Trauma, Burn and Combined Injury, Key Lab for Biomechanics and Tissue Engineering of Chongqing, Army Medical University (Third Military Medical University), Chongqing, 400038, ChinaDepartment of Anatomy, State Key Laboratory of Trauma, Burn and Combined Injury, Key Lab for Biomechanics and Tissue Engineering of Chongqing, Army Medical University (Third Military Medical University), Chongqing, 400038, ChinaDepartment of Anatomy, State Key Laboratory of Trauma, Burn and Combined Injury, Key Lab for Biomechanics and Tissue Engineering of Chongqing, Army Medical University (Third Military Medical University), Chongqing, 400038, ChinaDepartment of Anatomy, State Key Laboratory of Trauma, Burn and Combined Injury, Key Lab for Biomechanics and Tissue Engineering of Chongqing, Army Medical University (Third Military Medical University), Chongqing, 400038, ChinaDepartment of Anatomy, State Key Laboratory of Trauma, Burn and Combined Injury, Key Lab for Biomechanics and Tissue Engineering of Chongqing, Army Medical University (Third Military Medical University), Chongqing, 400038, China; Chongqing Institute of Zhong Zhi Yi Gu, Shapingba District, Chongqing, 400030, ChinaDepartment of Anatomy, State Key Laboratory of Trauma, Burn and Combined Injury, Key Lab for Biomechanics and Tissue Engineering of Chongqing, Army Medical University (Third Military Medical University), Chongqing, 400038, ChinaDepartment of Anatomy, State Key Laboratory of Trauma, Burn and Combined Injury, Key Lab for Biomechanics and Tissue Engineering of Chongqing, Army Medical University (Third Military Medical University), Chongqing, 400038, ChinaDepartment of Anatomy, State Key Laboratory of Trauma, Burn and Combined Injury, Key Lab for Biomechanics and Tissue Engineering of Chongqing, Army Medical University (Third Military Medical University), Chongqing, 400038, ChinaDepartment of Anatomy, State Key Laboratory of Trauma, Burn and Combined Injury, Key Lab for Biomechanics and Tissue Engineering of Chongqing, Army Medical University (Third Military Medical University), Chongqing, 400038, ChinaDepartment of Cell Biology, Third Military Army Medical University, Chongqing, 400038, China; Corresponding author.Department of Anatomy, State Key Laboratory of Trauma, Burn and Combined Injury, Key Lab for Biomechanics and Tissue Engineering of Chongqing, Army Medical University (Third Military Medical University), Chongqing, 400038, China; Corresponding author.Cell therapy has been a promising strategy for cardiac repair after myocardial infarction (MI), but a poor ischemic environment and low cell delivery efficiency remain significant challenges. The spleen serves as a hematopoietic stem cell niche and secretes cardioprotective factors after MI, but it is unclear whether it could be used for human pluripotent stem cell (hiPSC) cultivation and provide a proper microenvironment for cell grafts against the ischemic environment. Herein, we developed a splenic extracellular matrix derived thermoresponsive hydrogel (SpGel). Proteomics analysis indicated that SpGel is enriched with proteins known to modulate the Wnt signaling pathway, cell-substrate adhesion, cardiac muscle contraction and oxidation-reduction processes. In vitro studies demonstrated that hiPSCs could be efficiently induced into endothelial cells (iECs) and cardiomyocytes (iCMs) with enhanced function on SpGel. The cytoprotective effect of SpGel on iECs/iCMs against oxidative stress damage was also proven. Furthermore, in vivo studies revealed that iEC/iCM-laden SpGel improved cardiac function and inhibited cardiac fibrosis of infarcted hearts by improving cell survival, revascularization and remuscularization. In conclusion, we successfully established a novel platform for the efficient generation and delivery of autologous cell grafts, which could be a promising clinical therapeutic strategy for cardiac repair and regeneration after MI.http://www.sciencedirect.com/science/article/pii/S2452199X21001766Stem cell-laden splenic hydrogelhiPSC differentiation platformAntioxidant stressMyocardial infarctionCardiac repair |
| spellingShingle | Ge Guan Da Huo Yanzhao Li Xiaolin Zhao Yinghao Li Zhongliang Qin Dayu Sun Guanyuan Yang Mingcan Yang Ju Tan Wen Zeng Chuhong Zhu Engineering hiPSC-CM and hiPSC-EC laden 3D nanofibrous splenic hydrogel for improving cardiac function through revascularization and remuscularization in infarcted heart Bioactive Materials Stem cell-laden splenic hydrogel hiPSC differentiation platform Antioxidant stress Myocardial infarction Cardiac repair |
| title | Engineering hiPSC-CM and hiPSC-EC laden 3D nanofibrous splenic hydrogel for improving cardiac function through revascularization and remuscularization in infarcted heart |
| title_full | Engineering hiPSC-CM and hiPSC-EC laden 3D nanofibrous splenic hydrogel for improving cardiac function through revascularization and remuscularization in infarcted heart |
| title_fullStr | Engineering hiPSC-CM and hiPSC-EC laden 3D nanofibrous splenic hydrogel for improving cardiac function through revascularization and remuscularization in infarcted heart |
| title_full_unstemmed | Engineering hiPSC-CM and hiPSC-EC laden 3D nanofibrous splenic hydrogel for improving cardiac function through revascularization and remuscularization in infarcted heart |
| title_short | Engineering hiPSC-CM and hiPSC-EC laden 3D nanofibrous splenic hydrogel for improving cardiac function through revascularization and remuscularization in infarcted heart |
| title_sort | engineering hipsc cm and hipsc ec laden 3d nanofibrous splenic hydrogel for improving cardiac function through revascularization and remuscularization in infarcted heart |
| topic | Stem cell-laden splenic hydrogel hiPSC differentiation platform Antioxidant stress Myocardial infarction Cardiac repair |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X21001766 |
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