Programming of Regulatory T Cells In Situ for Nerve Regeneration and Long-Term Patency of Vascular Grafts
Rapid integration into the host tissue is critical for long-term patency after small diameter tissue engineering vascular grafts (sdTEVGs) transplantation. Neural recognition may be required for host integration and functionalization of the graft. However, immune rejection and inflammation hinder ne...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Association for the Advancement of Science (AAAS)
2022-01-01
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| Series: | Research |
| Online Access: | http://dx.doi.org/10.34133/2022/9826426 |
| _version_ | 1797287765176483840 |
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| author | Yanhong Wang Fangchao Xue Yanzhao Li Lin Lin Yeqin Wang Shanlan Zhao Xingli Zhao Yong Liu Ju Tan Gang Li Haoran Xiao Juan Yan Hao Tian Min Liu Qiao Zhang Zhaojing Ba Lang He Wenyan Zhao Chuhong Zhu Wen Zeng |
| author_facet | Yanhong Wang Fangchao Xue Yanzhao Li Lin Lin Yeqin Wang Shanlan Zhao Xingli Zhao Yong Liu Ju Tan Gang Li Haoran Xiao Juan Yan Hao Tian Min Liu Qiao Zhang Zhaojing Ba Lang He Wenyan Zhao Chuhong Zhu Wen Zeng |
| author_sort | Yanhong Wang |
| collection | DOAJ |
| description | Rapid integration into the host tissue is critical for long-term patency after small diameter tissue engineering vascular grafts (sdTEVGs) transplantation. Neural recognition may be required for host integration and functionalization of the graft. However, immune rejection and inflammation hinder nerve regeneration of sdTEVGs. Here, a CRISPR/dCas9-nanocarrier was used for targeted programming of regulatory T cells (Treg cells) in situ to promote nerve regeneration of sdTEVGs by preventing excessive inflammation. Treg cells and (C-C chemokine receptor) CCR2+ macrophage recruitment occurred after transplantation. The nanodelivery system upregulated ten eleven translocation (TET2) in Treg cells in vitro. Reprogrammed Treg cells upregulated anti-inflammatory cytokines and decreased the proportion of CCR2+ macrophages. IL-6 concentrations decreased to the levels required for nerve regeneration. Implantation of CRISPR/dCas9 nanodelivery system-modified sdTEVGs in rats resulted in Treg cell editing, control of excessive inflammation, and promoted nerve regeneration. After 3 months, nerve regeneration was similar to that observed in normal blood vessels; good immune homeostasis, consistency of hemodynamics, and matrix regeneration were observed. Neural recognition promotes further integration of the graft into the host, with unobstructed blood vessels without intimal hyperplasia. Our findings provide new insights into vascular implant functionalization by the host. |
| first_indexed | 2024-03-07T18:39:24Z |
| format | Article |
| id | doaj.art-7f9a9631915242bab54e31fac83d4cf9 |
| institution | Directory Open Access Journal |
| issn | 2639-5274 |
| language | English |
| last_indexed | 2024-03-07T18:39:24Z |
| publishDate | 2022-01-01 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | Article |
| series | Research |
| spelling | doaj.art-7f9a9631915242bab54e31fac83d4cf92024-03-02T04:24:56ZengAmerican Association for the Advancement of Science (AAAS)Research2639-52742022-01-01202210.34133/2022/9826426Programming of Regulatory T Cells In Situ for Nerve Regeneration and Long-Term Patency of Vascular GraftsYanhong Wang0Fangchao Xue1Yanzhao Li2Lin Lin3Yeqin Wang4Shanlan Zhao5Xingli Zhao6Yong Liu7Ju Tan8Gang Li9Haoran Xiao10Juan Yan11Hao Tian12Min Liu13Qiao Zhang14Zhaojing Ba15Lang He16Wenyan Zhao17Chuhong Zhu18Wen Zeng19Department of Cell Biology, Third Military Army Medical University, Chongqing 400038, ChinaDepartment of Cell Biology, Third Military Army Medical University, Chongqing 400038, ChinaDepartment of Anatomy, National and Regional Engineering Laboratory of Tissue Engineering, State and Local Joint Engineering Laboratory for Vascular Implants, Key Lab for Biomechanics and Tissue Engineering of Chongqing, Third Military Medical University, Chongqing 400038, ChinaDepartment of Cell Biology, Third Military Army Medical University, Chongqing 400038, ChinaDepartment of Cell Biology, Third Military Army Medical University, Chongqing 400038, ChinaDepartment of Cell Biology, Third Military Army Medical University, Chongqing 400038, ChinaDepartment of Cell Biology, Third Military Army Medical University, Chongqing 400038, ChinaDepartment of Anatomy, National and Regional Engineering Laboratory of Tissue Engineering, State and Local Joint Engineering Laboratory for Vascular Implants, Key Lab for Biomechanics and Tissue Engineering of Chongqing, Third Military Medical University, Chongqing 400038, ChinaDepartment of Anatomy, National and Regional Engineering Laboratory of Tissue Engineering, State and Local Joint Engineering Laboratory for Vascular Implants, Key Lab for Biomechanics and Tissue Engineering of Chongqing, Third Military Medical University, Chongqing 400038, ChinaDepartment of Anatomy, National and Regional Engineering Laboratory of Tissue Engineering, State and Local Joint Engineering Laboratory for Vascular Implants, Key Lab for Biomechanics and Tissue Engineering of Chongqing, Third Military Medical University, Chongqing 400038, ChinaDepartment of Cell Biology, Third Military Army Medical University, Chongqing 400038, ChinaDepartment of Cell Biology, Third Military Army Medical University, Chongqing 400038, ChinaDepartment of Cell Biology, Third Military Army Medical University, Chongqing 400038, ChinaDepartment of Cell Biology, Third Military Army Medical University, Chongqing 400038, ChinaDepartment of Cell Biology, Third Military Army Medical University, Chongqing 400038, ChinaDepartment of Cell Biology, Third Military Army Medical University, Chongqing 400038, ChinaDepartment of Cell Biology, Third Military Army Medical University, Chongqing 400038, ChinaDepartment of Cell Biology, Third Military Army Medical University, Chongqing 400038, ChinaDepartment of Anatomy, National and Regional Engineering Laboratory of Tissue Engineering, State and Local Joint Engineering Laboratory for Vascular Implants, Key Lab for Biomechanics and Tissue Engineering of Chongqing, Third Military Medical University, Chongqing 400038, ChinaDepartment of Cell Biology, Third Military Army Medical University, Chongqing 400038, China; State Key Laboratory of Trauma, Burn and Combined Injury, Chongqing, China; Departments of Neurology, Southwest Hospital, Third Military Medical University, Chongqing, ChinaRapid integration into the host tissue is critical for long-term patency after small diameter tissue engineering vascular grafts (sdTEVGs) transplantation. Neural recognition may be required for host integration and functionalization of the graft. However, immune rejection and inflammation hinder nerve regeneration of sdTEVGs. Here, a CRISPR/dCas9-nanocarrier was used for targeted programming of regulatory T cells (Treg cells) in situ to promote nerve regeneration of sdTEVGs by preventing excessive inflammation. Treg cells and (C-C chemokine receptor) CCR2+ macrophage recruitment occurred after transplantation. The nanodelivery system upregulated ten eleven translocation (TET2) in Treg cells in vitro. Reprogrammed Treg cells upregulated anti-inflammatory cytokines and decreased the proportion of CCR2+ macrophages. IL-6 concentrations decreased to the levels required for nerve regeneration. Implantation of CRISPR/dCas9 nanodelivery system-modified sdTEVGs in rats resulted in Treg cell editing, control of excessive inflammation, and promoted nerve regeneration. After 3 months, nerve regeneration was similar to that observed in normal blood vessels; good immune homeostasis, consistency of hemodynamics, and matrix regeneration were observed. Neural recognition promotes further integration of the graft into the host, with unobstructed blood vessels without intimal hyperplasia. Our findings provide new insights into vascular implant functionalization by the host.http://dx.doi.org/10.34133/2022/9826426 |
| spellingShingle | Yanhong Wang Fangchao Xue Yanzhao Li Lin Lin Yeqin Wang Shanlan Zhao Xingli Zhao Yong Liu Ju Tan Gang Li Haoran Xiao Juan Yan Hao Tian Min Liu Qiao Zhang Zhaojing Ba Lang He Wenyan Zhao Chuhong Zhu Wen Zeng Programming of Regulatory T Cells In Situ for Nerve Regeneration and Long-Term Patency of Vascular Grafts Research |
| title | Programming of Regulatory T Cells In Situ for Nerve Regeneration and Long-Term Patency of Vascular Grafts |
| title_full | Programming of Regulatory T Cells In Situ for Nerve Regeneration and Long-Term Patency of Vascular Grafts |
| title_fullStr | Programming of Regulatory T Cells In Situ for Nerve Regeneration and Long-Term Patency of Vascular Grafts |
| title_full_unstemmed | Programming of Regulatory T Cells In Situ for Nerve Regeneration and Long-Term Patency of Vascular Grafts |
| title_short | Programming of Regulatory T Cells In Situ for Nerve Regeneration and Long-Term Patency of Vascular Grafts |
| title_sort | programming of regulatory t cells in situ for nerve regeneration and long term patency of vascular grafts |
| url | http://dx.doi.org/10.34133/2022/9826426 |
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