CD31 defines a subpopulation of human adipose-derived regenerative cells with potent angiogenic effects
Abstract 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 involvin...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-09-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-41535-1 |
| _version_ | 1797559839795183616 |
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| author | Pratibha Dhumale Jakob Vennike Nielsen Anne Cathrine Schmidt Hansen Mark Burton Hans Christian Beck Mads Gustaf Jørgensen Navid Mohamadpour Toyserkani Martha Kirstine Haahr Sabrina Toft Hansen Lars Lund Mads Thomassen Jens Ahm Sørensen Ditte Caroline Andersen Charlotte Harken Jensen Søren Paludan Sheikh |
| author_facet | Pratibha Dhumale Jakob Vennike Nielsen Anne Cathrine Schmidt Hansen Mark Burton Hans Christian Beck Mads Gustaf Jørgensen Navid Mohamadpour Toyserkani Martha Kirstine Haahr Sabrina Toft Hansen Lars Lund Mads Thomassen Jens Ahm Sørensen Ditte Caroline Andersen Charlotte Harken Jensen Søren Paludan Sheikh |
| author_sort | Pratibha Dhumale |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-10T17:50:59Z |
| format | Article |
| id | doaj.art-8349d1f1a861482c933e74589114bbd7 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-10T17:50:59Z |
| publishDate | 2023-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-8349d1f1a861482c933e74589114bbd72023-11-20T09:21:11ZengNature PortfolioScientific Reports2045-23222023-09-0113111710.1038/s41598-023-41535-1CD31 defines a subpopulation of human adipose-derived regenerative cells with potent angiogenic effectsPratibha Dhumale0Jakob Vennike Nielsen1Anne Cathrine Schmidt Hansen2Mark Burton3Hans Christian Beck4Mads Gustaf Jørgensen5Navid Mohamadpour Toyserkani6Martha Kirstine Haahr7Sabrina Toft Hansen8Lars Lund9Mads Thomassen10Jens Ahm Sørensen11Ditte Caroline Andersen12Charlotte Harken Jensen13Søren Paludan Sheikh14Department of Clinical Research, University of Southern Denmark (SDU)Department of Clinical Biochemistry, Odense University Hospital (OUH)Department of Clinical Biochemistry, Odense University Hospital (OUH)Department of Clinical Genetics, OUHDepartment of Clinical Research, University of Southern Denmark (SDU)Department of Clinical Research, University of Southern Denmark (SDU)Department of Plastic Surgery, OUHDepartment of Urology, OUHDepartment of Clinical Research, University of Southern Denmark (SDU)Department of Clinical Research, University of Southern Denmark (SDU)Department of Clinical Research, University of Southern Denmark (SDU)Department of Clinical Research, University of Southern Denmark (SDU)Department of Clinical Research, University of Southern Denmark (SDU)Department of Clinical Research, University of Southern Denmark (SDU)Department of Clinical Research, University of Southern Denmark (SDU)Abstract 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.https://doi.org/10.1038/s41598-023-41535-1 |
| spellingShingle | Pratibha Dhumale Jakob Vennike Nielsen Anne Cathrine Schmidt Hansen Mark Burton Hans Christian Beck Mads Gustaf Jørgensen Navid Mohamadpour Toyserkani Martha Kirstine Haahr Sabrina Toft Hansen Lars Lund Mads Thomassen Jens Ahm Sørensen Ditte Caroline Andersen Charlotte Harken Jensen Søren Paludan Sheikh CD31 defines a subpopulation of human adipose-derived regenerative cells with potent angiogenic effects Scientific Reports |
| 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 |
| url | https://doi.org/10.1038/s41598-023-41535-1 |
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