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CD31 defines a subpopulation of human adipose-derived regenerative cells with potent angiogenic effects
Cellular heterogeneity represents a major challenge for regenerative treatment using freshly isolated Adipose Derived Regenerative Cells (ADRCs). Emerging data suggest superior efficacy of ADRCs as compared to the ex vivo expanded and more homogeneous ADRCs (= ASCs) for indications involving (micro)...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10474028/ https://www.ncbi.nlm.nih.gov/pubmed/37658225 http://dx.doi.org/10.1038/s41598-023-41535-1 |
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author | Dhumale, Pratibha Nielsen, Jakob Vennike Hansen, Anne Cathrine Schmidt Burton, Mark Beck, Hans Christian Jørgensen, Mads Gustaf Toyserkani, Navid Mohamadpour Haahr, Martha Kirstine Hansen, Sabrina Toft Lund, Lars Thomassen, Mads Sørensen, Jens Ahm Andersen, Ditte Caroline Jensen, Charlotte Harken Sheikh, Søren Paludan |
author_facet | Dhumale, Pratibha Nielsen, Jakob Vennike Hansen, Anne Cathrine Schmidt Burton, Mark Beck, Hans Christian Jørgensen, Mads Gustaf Toyserkani, Navid Mohamadpour Haahr, Martha Kirstine Hansen, Sabrina Toft Lund, Lars Thomassen, Mads Sørensen, Jens Ahm Andersen, Ditte Caroline Jensen, Charlotte Harken Sheikh, Søren Paludan |
author_sort | Dhumale, Pratibha |
collection | PubMed |
description | Cellular heterogeneity represents a major challenge for regenerative treatment using freshly isolated Adipose Derived Regenerative Cells (ADRCs). Emerging data suggest superior efficacy of ADRCs as compared to the ex vivo expanded and more homogeneous ADRCs (= ASCs) for indications involving (micro)vascular deficiency, however, it remains unknown which ADRC cell subtypes account for the improvement. Surprisingly, we found regarding erectile dysfunction (ED) that the number of injected CD31+ ADRCs correlated positively with erectile function 12 months after one bolus of autologous ADRCs. Comprehensive in vitro and ex vivo analyses confirmed superior pro-angiogenic and paracrine effects of human CD31+ enriched ADRCs compared to the corresponding CD31− and parent ADRCs. When CD31+, CD31− and ADRCs were co-cultured in aortic ring- and corpus cavernous tube formation assays, the CD31+ ADRCs induced significantly higher tube development. This effect was corroborated using conditioned medium (CM), while quantitative mass spectrometric analysis suggested that this is likely explained by secretory pro-angiogenic proteins including DKK3, ANGPT2, ANAX2 and VIM, all enriched in CD31+ ADRC CM. Single-cell RNA sequencing showed that transcripts of the upregulated and secreted proteins were present in 9 endothelial ADRC subsets including endothelial progenitor cells in the heterogenous non-cultured ADRCs. Our data suggest that the vascular benefit of using ADRCs in regenerative medicine is dictated by CD31+ ADRCs. |
format | Online Article Text |
id | pubmed-10474028 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-104740282023-09-03 CD31 defines a subpopulation of human adipose-derived regenerative cells with potent angiogenic effects Dhumale, Pratibha Nielsen, Jakob Vennike Hansen, Anne Cathrine Schmidt Burton, Mark Beck, Hans Christian Jørgensen, Mads Gustaf Toyserkani, Navid Mohamadpour Haahr, Martha Kirstine Hansen, Sabrina Toft Lund, Lars Thomassen, Mads Sørensen, Jens Ahm Andersen, Ditte Caroline Jensen, Charlotte Harken Sheikh, Søren Paludan Sci Rep Article Cellular heterogeneity represents a major challenge for regenerative treatment using freshly isolated Adipose Derived Regenerative Cells (ADRCs). Emerging data suggest superior efficacy of ADRCs as compared to the ex vivo expanded and more homogeneous ADRCs (= ASCs) for indications involving (micro)vascular deficiency, however, it remains unknown which ADRC cell subtypes account for the improvement. Surprisingly, we found regarding erectile dysfunction (ED) that the number of injected CD31+ ADRCs correlated positively with erectile function 12 months after one bolus of autologous ADRCs. Comprehensive in vitro and ex vivo analyses confirmed superior pro-angiogenic and paracrine effects of human CD31+ enriched ADRCs compared to the corresponding CD31− and parent ADRCs. When CD31+, CD31− and ADRCs were co-cultured in aortic ring- and corpus cavernous tube formation assays, the CD31+ ADRCs induced significantly higher tube development. This effect was corroborated using conditioned medium (CM), while quantitative mass spectrometric analysis suggested that this is likely explained by secretory pro-angiogenic proteins including DKK3, ANGPT2, ANAX2 and VIM, all enriched in CD31+ ADRC CM. Single-cell RNA sequencing showed that transcripts of the upregulated and secreted proteins were present in 9 endothelial ADRC subsets including endothelial progenitor cells in the heterogenous non-cultured ADRCs. Our data suggest that the vascular benefit of using ADRCs in regenerative medicine is dictated by CD31+ ADRCs. Nature Publishing Group UK 2023-09-01 /pmc/articles/PMC10474028/ /pubmed/37658225 http://dx.doi.org/10.1038/s41598-023-41535-1 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This 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/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Dhumale, Pratibha Nielsen, Jakob Vennike Hansen, Anne Cathrine Schmidt Burton, Mark Beck, Hans Christian Jørgensen, Mads Gustaf Toyserkani, Navid Mohamadpour Haahr, Martha Kirstine Hansen, Sabrina Toft Lund, Lars Thomassen, Mads Sørensen, Jens Ahm Andersen, Ditte Caroline Jensen, Charlotte Harken Sheikh, Søren Paludan CD31 defines a subpopulation of human adipose-derived regenerative cells with potent angiogenic effects |
title | CD31 defines a subpopulation of human adipose-derived regenerative cells with potent angiogenic effects |
title_full | CD31 defines a subpopulation of human adipose-derived regenerative cells with potent angiogenic effects |
title_fullStr | CD31 defines a subpopulation of human adipose-derived regenerative cells with potent angiogenic effects |
title_full_unstemmed | CD31 defines a subpopulation of human adipose-derived regenerative cells with potent angiogenic effects |
title_short | CD31 defines a subpopulation of human adipose-derived regenerative cells with potent angiogenic effects |
title_sort | cd31 defines a subpopulation of human adipose-derived regenerative cells with potent angiogenic effects |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10474028/ https://www.ncbi.nlm.nih.gov/pubmed/37658225 http://dx.doi.org/10.1038/s41598-023-41535-1 |
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