Immune-mediated regeneration of cell-free vascular grafts in an ovine model

Abstract We developed acellular tissue engineered vessels (ATEV) using small intestine submucosa (SIS) incorporating heparin and a novel protein named H2R5. ATEVs were implanted into the arterial circulation of an ovine animal model, demonstrating high primary patency rates over a period of three mo...

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Main Authors: Bita Nasiri, Arundhati Das, Karthik Ramachandran, Sai Harsha Bhamidipati, Yulun Wu, Shriramprasad Venkatesan, Rudiyanto Gunawan, Daniel D. Swartz, Stelios T. Andreadis
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:npj Regenerative Medicine
Online Access:https://doi.org/10.1038/s41536-025-00400-7
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author Bita Nasiri
Arundhati Das
Karthik Ramachandran
Sai Harsha Bhamidipati
Yulun Wu
Shriramprasad Venkatesan
Rudiyanto Gunawan
Daniel D. Swartz
Stelios T. Andreadis
author_facet Bita Nasiri
Arundhati Das
Karthik Ramachandran
Sai Harsha Bhamidipati
Yulun Wu
Shriramprasad Venkatesan
Rudiyanto Gunawan
Daniel D. Swartz
Stelios T. Andreadis
author_sort Bita Nasiri
collection DOAJ
description Abstract We developed acellular tissue engineered vessels (ATEV) using small intestine submucosa (SIS) incorporating heparin and a novel protein named H2R5. ATEVs were implanted into the arterial circulation of an ovine animal model, demonstrating high primary patency rates over a period of three months. Implanted grafts were infiltrated by host cells, the majority of which were monocytes/macrophages (MC/MΦ), as demonstrated by scRNA sequencing and immunostaining. They also developed functional endothelial and medial layers that deposited new extracellular matrix leading to matrix remodeling and acquisition of mechanical properties that were similar to those of native arteries. Notably, during this short implantation time, ATEVs turned into functional neo-arteries, as evidenced by the development of the vascular contractile function. Our findings underscore the potential of H2R5-functionalized ATEVs as promising candidates for tissue replacement grafts in a large pre-clinical animal model and highlight the contribution of macrophages in vascular regeneration.
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institution Kabale University
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publishDate 2025-03-01
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series npj Regenerative Medicine
spelling doaj-art-1677f3dd9a5b4f4590cebcfbdc4940472025-08-20T03:41:46ZengNature Portfolionpj Regenerative Medicine2057-39952025-03-0110111510.1038/s41536-025-00400-7Immune-mediated regeneration of cell-free vascular grafts in an ovine modelBita Nasiri0Arundhati Das1Karthik Ramachandran2Sai Harsha Bhamidipati3Yulun Wu4Shriramprasad Venkatesan5Rudiyanto Gunawan6Daniel D. Swartz7Stelios T. Andreadis8Department of Chemical and Biological Engineering, University at Buffalo, The State University of New YorkDepartment of Chemical and Biological Engineering, University at Buffalo, The State University of New YorkDepartment of Chemical and Biological Engineering, University at Buffalo, The State University of New YorkDepartment of Chemical and Biological Engineering, University at Buffalo, The State University of New YorkDepartment of Chemical and Biological Engineering, University at Buffalo, The State University of New YorkDepartment of Chemical and Biological Engineering, University at Buffalo, The State University of New YorkDepartment of Chemical and Biological Engineering, University at Buffalo, The State University of New YorkAngiograft LLCDepartment of Chemical and Biological Engineering, University at Buffalo, The State University of New YorkAbstract We developed acellular tissue engineered vessels (ATEV) using small intestine submucosa (SIS) incorporating heparin and a novel protein named H2R5. ATEVs were implanted into the arterial circulation of an ovine animal model, demonstrating high primary patency rates over a period of three months. Implanted grafts were infiltrated by host cells, the majority of which were monocytes/macrophages (MC/MΦ), as demonstrated by scRNA sequencing and immunostaining. They also developed functional endothelial and medial layers that deposited new extracellular matrix leading to matrix remodeling and acquisition of mechanical properties that were similar to those of native arteries. Notably, during this short implantation time, ATEVs turned into functional neo-arteries, as evidenced by the development of the vascular contractile function. Our findings underscore the potential of H2R5-functionalized ATEVs as promising candidates for tissue replacement grafts in a large pre-clinical animal model and highlight the contribution of macrophages in vascular regeneration.https://doi.org/10.1038/s41536-025-00400-7
spellingShingle Bita Nasiri
Arundhati Das
Karthik Ramachandran
Sai Harsha Bhamidipati
Yulun Wu
Shriramprasad Venkatesan
Rudiyanto Gunawan
Daniel D. Swartz
Stelios T. Andreadis
Immune-mediated regeneration of cell-free vascular grafts in an ovine model
npj Regenerative Medicine
title Immune-mediated regeneration of cell-free vascular grafts in an ovine model
title_full Immune-mediated regeneration of cell-free vascular grafts in an ovine model
title_fullStr Immune-mediated regeneration of cell-free vascular grafts in an ovine model
title_full_unstemmed Immune-mediated regeneration of cell-free vascular grafts in an ovine model
title_short Immune-mediated regeneration of cell-free vascular grafts in an ovine model
title_sort immune mediated regeneration of cell free vascular grafts in an ovine model
url https://doi.org/10.1038/s41536-025-00400-7
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AT saiharshabhamidipati immunemediatedregenerationofcellfreevasculargraftsinanovinemodel
AT yulunwu immunemediatedregenerationofcellfreevasculargraftsinanovinemodel
AT shriramprasadvenkatesan immunemediatedregenerationofcellfreevasculargraftsinanovinemodel
AT rudiyantogunawan immunemediatedregenerationofcellfreevasculargraftsinanovinemodel
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