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Adipose-derived cellular therapies prolong graft survival in an allogenic hind limb transplantation model
BACKGROUND: The long-term survival after vascularized composite allotransplantation (VCA) is often limited by systemic rejection as well as the adverse effects of immunosuppressants. The stromal vascular fraction (SVF) can be expanded to produce adipose-derived stem cells (ADSC) which represents a c...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847016/ https://www.ncbi.nlm.nih.gov/pubmed/33514430 http://dx.doi.org/10.1186/s13287-021-02162-7 |
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author | Chen, Jingting Wang, Yinmin Hu, Haoyue Xiong, Yao Wang, Shoubao Yang, Jun |
author_facet | Chen, Jingting Wang, Yinmin Hu, Haoyue Xiong, Yao Wang, Shoubao Yang, Jun |
author_sort | Chen, Jingting |
collection | PubMed |
description | BACKGROUND: The long-term survival after vascularized composite allotransplantation (VCA) is often limited by systemic rejection as well as the adverse effects of immunosuppressants. The stromal vascular fraction (SVF) can be expanded to produce adipose-derived stem cells (ADSC) which represents a combination of endothelial cells, preadipocytes, immune cells, and ADSC. It has been demonstrated that ADSC possess consistently reliable clinical results. However, literature is scarce regarding SVF in VCA. This study seeks to determine the impact of ex vivo allograft pretreatment in combination with SVF cells in the ability to promote composite tissue allotransplantation immunotolerance. METHODS: A rat hind limb allotransplant model was used to investigate the influence of ex vivo pretreatment of SVF and ADSC on VCA survival. Intravascular cell-free saline, ADSC, or SVF was infused into the models with immunosuppressants. The histopathological examination and duration that the allografts went without displaying symptoms of rejection was documented. Peripheral T lymphocytes and Tregs were quantified with flow cytometry while allotissue expressions of CD31 were quantified with immunohistochemical staining (IHC). ELISA was used to detect vascular endothelial growth factor (VEGF)-A as well as anti- and pro-inflammatory cytokines. RESULTS: We demonstrated that ex vivo treatment of allografts with SVF or ADSC prolonged allograft survival in contrast to medium control cohorts. There were also enhanced levels of immunomodulatory cytokines and increased VEGF-A and CD31 expression as well as reduced infiltration and proliferation of T lymphocytes along with raised Treg expressions. CONCLUSION: These studies demonstrated that adipose-derived cellular therapies prolong graft survival in an allogenic hind limb transplantation model and have the potential to establish immunotolerance. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-021-02162-7. |
format | Online Article Text |
id | pubmed-7847016 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-78470162021-02-01 Adipose-derived cellular therapies prolong graft survival in an allogenic hind limb transplantation model Chen, Jingting Wang, Yinmin Hu, Haoyue Xiong, Yao Wang, Shoubao Yang, Jun Stem Cell Res Ther Research BACKGROUND: The long-term survival after vascularized composite allotransplantation (VCA) is often limited by systemic rejection as well as the adverse effects of immunosuppressants. The stromal vascular fraction (SVF) can be expanded to produce adipose-derived stem cells (ADSC) which represents a combination of endothelial cells, preadipocytes, immune cells, and ADSC. It has been demonstrated that ADSC possess consistently reliable clinical results. However, literature is scarce regarding SVF in VCA. This study seeks to determine the impact of ex vivo allograft pretreatment in combination with SVF cells in the ability to promote composite tissue allotransplantation immunotolerance. METHODS: A rat hind limb allotransplant model was used to investigate the influence of ex vivo pretreatment of SVF and ADSC on VCA survival. Intravascular cell-free saline, ADSC, or SVF was infused into the models with immunosuppressants. The histopathological examination and duration that the allografts went without displaying symptoms of rejection was documented. Peripheral T lymphocytes and Tregs were quantified with flow cytometry while allotissue expressions of CD31 were quantified with immunohistochemical staining (IHC). ELISA was used to detect vascular endothelial growth factor (VEGF)-A as well as anti- and pro-inflammatory cytokines. RESULTS: We demonstrated that ex vivo treatment of allografts with SVF or ADSC prolonged allograft survival in contrast to medium control cohorts. There were also enhanced levels of immunomodulatory cytokines and increased VEGF-A and CD31 expression as well as reduced infiltration and proliferation of T lymphocytes along with raised Treg expressions. CONCLUSION: These studies demonstrated that adipose-derived cellular therapies prolong graft survival in an allogenic hind limb transplantation model and have the potential to establish immunotolerance. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-021-02162-7. BioMed Central 2021-01-29 /pmc/articles/PMC7847016/ /pubmed/33514430 http://dx.doi.org/10.1186/s13287-021-02162-7 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Chen, Jingting Wang, Yinmin Hu, Haoyue Xiong, Yao Wang, Shoubao Yang, Jun Adipose-derived cellular therapies prolong graft survival in an allogenic hind limb transplantation model |
title | Adipose-derived cellular therapies prolong graft survival in an allogenic hind limb transplantation model |
title_full | Adipose-derived cellular therapies prolong graft survival in an allogenic hind limb transplantation model |
title_fullStr | Adipose-derived cellular therapies prolong graft survival in an allogenic hind limb transplantation model |
title_full_unstemmed | Adipose-derived cellular therapies prolong graft survival in an allogenic hind limb transplantation model |
title_short | Adipose-derived cellular therapies prolong graft survival in an allogenic hind limb transplantation model |
title_sort | adipose-derived cellular therapies prolong graft survival in an allogenic hind limb transplantation model |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847016/ https://www.ncbi.nlm.nih.gov/pubmed/33514430 http://dx.doi.org/10.1186/s13287-021-02162-7 |
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