Cord blood-endothelial colony forming cells are immunotolerated and participate at post-ischemic angiogenesis in an original dorsal chamber immunocompetent mouse model
Abstract Background Cardiovascular diseases are the main cause of morbidity and mortality worldwide. Restoring blood supply to ischemic tissues is an essential goal for the successful treatment of these diseases. Growth factor or gene therapy efficacy remains controversial, but stem cell transplanta...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-05-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13287-020-01687-7 |
| _version_ | 1811299522406514688 |
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| author | Richard Proust Anne-Charlotte Ponsen Valérie Rouffiac Chantal Schenowitz Florent Montespan Karine Ser-Le Roux Frédéric De Leeuw Corinne Laplace-Builhé Philippe Mauduit Edgardo D. Carosella Sébastien Banzet Jean-Jacques Lataillade Nathalie Rouas-Freiss Georges Uzan Juliette Peltzer |
| author_facet | Richard Proust Anne-Charlotte Ponsen Valérie Rouffiac Chantal Schenowitz Florent Montespan Karine Ser-Le Roux Frédéric De Leeuw Corinne Laplace-Builhé Philippe Mauduit Edgardo D. Carosella Sébastien Banzet Jean-Jacques Lataillade Nathalie Rouas-Freiss Georges Uzan Juliette Peltzer |
| author_sort | Richard Proust |
| collection | DOAJ |
| description | Abstract Background Cardiovascular diseases are the main cause of morbidity and mortality worldwide. Restoring blood supply to ischemic tissues is an essential goal for the successful treatment of these diseases. Growth factor or gene therapy efficacy remains controversial, but stem cell transplantation is emerging as an interesting approach to stimulate angiogenesis. Among the different stem cell populations, cord blood-endothelial progenitor cells (CB-EPCs) and more particularly cord blood-endothelial progenitor cell-derived endothelial colony forming cells (CB-ECFCs) have a great proliferative potential without exhibiting signs of senescence. Even if it was already described that CB-ECFCs were able to restore blood perfusion in hind-limb ischemia in an immunodeficient mouse model, until now, the immunogenic potential of allogenic CB-ECFCs remains controversial. Therefore, our objectives were to evaluate the immune tolerance potency of CB-ECFCs and their capacity to restore a functional vascular network under ischemic condition in immunocompetent mice. Methods In vitro, the expression and secretion of immunoregulatory markers (HLA-G, IL-10, and TGF-β1) were evaluated on CB-ECFCs. Moreover, CB-ECFCs were co-cultured with activated peripheral blood mononuclear cells (PBMCs) for 6 days. PBMC proliferation was evaluated by [3H]-thymidine incorporation on the last 18 h. In vivo, CB-ECFCs were administered in the spleen and muscle of immunocompetent mice. Tissues were collected at day 14 after surgery. Finally, CB-ECFCs were injected intradermally in C57BL/6JRj mice close to ischemic macrovessel induced by thermal cauterization. Mice recovered until day 5 and were imaged, twice a week until day 30. Results Firstly, we demonstrated that CB-ECFCs expressed HLA-G, IL-10, and TGF-β1 and secreted IL-10 and TGF-β1 and that they could display immunosuppressive properties in vitro. Secondly, we showed that CB-ECFCs could be tolerated until 14 days in immunocompetent mice. Thirdly, we revealed in an original ischemic model of dorsal chamber that CB-ECFCs were integrated in a new functional vascular network. Conclusion These results open up new perspectives about using CB-ECFCs as an allogeneic cell therapy product and gives new impulse to the treatment of cardiovascular diseases. |
| first_indexed | 2024-04-13T06:36:10Z |
| format | Article |
| id | doaj.art-0194969ff25544469d73275cc587a140 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-04-13T06:36:10Z |
| publishDate | 2020-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-0194969ff25544469d73275cc587a1402022-12-22T02:57:53ZengBMCStem Cell Research & Therapy1757-65122020-05-0111111310.1186/s13287-020-01687-7Cord blood-endothelial colony forming cells are immunotolerated and participate at post-ischemic angiogenesis in an original dorsal chamber immunocompetent mouse modelRichard Proust0Anne-Charlotte Ponsen1Valérie Rouffiac2Chantal Schenowitz3Florent Montespan4Karine Ser-Le Roux5Frédéric De Leeuw6Corinne Laplace-Builhé7Philippe Mauduit8Edgardo D. Carosella9Sébastien Banzet10Jean-Jacques Lataillade11Nathalie Rouas-Freiss12Georges Uzan13Juliette Peltzer14INSERM UMR-S-MD 1197/Ministry of the Armed Forces, Biomedical Research Institut of the Armed Forces (IRBA), Paul-Brousse Hospital Villejuif and CTSA ClamartINSERM UMR-S-MD 1197/Ministry of the Armed Forces, Biomedical Research Institut of the Armed Forces (IRBA), Paul-Brousse Hospital Villejuif and CTSA ClamartParis-Saclay University, Paris-Sud University, Gustave Roussy Institute, INSERM, CNRS, Molecular Analysis, Modeling and Imaging of Cancer DiseaseCEA, DRF-IBFJ, Hemato-Immunology Research Unit, INSERM UMR-S 976, IRSL – Paris University, Saint-Louis HospitalINSERM UMR-S-MD 1197/Ministry of the Armed Forces, Biomedical Research Institut of the Armed Forces (IRBA), Paul-Brousse Hospital Villejuif and CTSA ClamartParis-Saclay University, Paris-Sud University, Gustave Roussy Institute, INSERM, CNRS, Molecular Analysis, Modeling and Imaging of Cancer DiseaseParis-Saclay University, Paris-Sud University, Gustave Roussy Institute, INSERM, CNRS, Molecular Analysis, Modeling and Imaging of Cancer DiseaseParis-Saclay University, Paris-Sud University, Gustave Roussy Institute, INSERM, CNRS, Molecular Analysis, Modeling and Imaging of Cancer DiseaseINSERM UMR-S-MD 1197/Ministry of the Armed Forces, Biomedical Research Institut of the Armed Forces (IRBA), Paul-Brousse Hospital Villejuif and CTSA ClamartCEA, DRF-IBFJ, Hemato-Immunology Research Unit, INSERM UMR-S 976, IRSL – Paris University, Saint-Louis HospitalINSERM UMR-S-MD 1197/Ministry of the Armed Forces, Biomedical Research Institut of the Armed Forces (IRBA), Paul-Brousse Hospital Villejuif and CTSA ClamartINSERM UMR-S-MD 1197/Ministry of the Armed Forces, Biomedical Research Institut of the Armed Forces (IRBA), Paul-Brousse Hospital Villejuif and CTSA ClamartCEA, DRF-IBFJ, Hemato-Immunology Research Unit, INSERM UMR-S 976, IRSL – Paris University, Saint-Louis HospitalINSERM UMR-S-MD 1197/Ministry of the Armed Forces, Biomedical Research Institut of the Armed Forces (IRBA), Paul-Brousse Hospital Villejuif and CTSA ClamartINSERM UMR-S-MD 1197/Ministry of the Armed Forces, Biomedical Research Institut of the Armed Forces (IRBA), Paul-Brousse Hospital Villejuif and CTSA ClamartAbstract Background Cardiovascular diseases are the main cause of morbidity and mortality worldwide. Restoring blood supply to ischemic tissues is an essential goal for the successful treatment of these diseases. Growth factor or gene therapy efficacy remains controversial, but stem cell transplantation is emerging as an interesting approach to stimulate angiogenesis. Among the different stem cell populations, cord blood-endothelial progenitor cells (CB-EPCs) and more particularly cord blood-endothelial progenitor cell-derived endothelial colony forming cells (CB-ECFCs) have a great proliferative potential without exhibiting signs of senescence. Even if it was already described that CB-ECFCs were able to restore blood perfusion in hind-limb ischemia in an immunodeficient mouse model, until now, the immunogenic potential of allogenic CB-ECFCs remains controversial. Therefore, our objectives were to evaluate the immune tolerance potency of CB-ECFCs and their capacity to restore a functional vascular network under ischemic condition in immunocompetent mice. Methods In vitro, the expression and secretion of immunoregulatory markers (HLA-G, IL-10, and TGF-β1) were evaluated on CB-ECFCs. Moreover, CB-ECFCs were co-cultured with activated peripheral blood mononuclear cells (PBMCs) for 6 days. PBMC proliferation was evaluated by [3H]-thymidine incorporation on the last 18 h. In vivo, CB-ECFCs were administered in the spleen and muscle of immunocompetent mice. Tissues were collected at day 14 after surgery. Finally, CB-ECFCs were injected intradermally in C57BL/6JRj mice close to ischemic macrovessel induced by thermal cauterization. Mice recovered until day 5 and were imaged, twice a week until day 30. Results Firstly, we demonstrated that CB-ECFCs expressed HLA-G, IL-10, and TGF-β1 and secreted IL-10 and TGF-β1 and that they could display immunosuppressive properties in vitro. Secondly, we showed that CB-ECFCs could be tolerated until 14 days in immunocompetent mice. Thirdly, we revealed in an original ischemic model of dorsal chamber that CB-ECFCs were integrated in a new functional vascular network. Conclusion These results open up new perspectives about using CB-ECFCs as an allogeneic cell therapy product and gives new impulse to the treatment of cardiovascular diseases.http://link.springer.com/article/10.1186/s13287-020-01687-7Endothelial progenitor cellsCord blood-endothelial colony forming cellsImmunotoleranceIschemiaAngiogenesis |
| spellingShingle | Richard Proust Anne-Charlotte Ponsen Valérie Rouffiac Chantal Schenowitz Florent Montespan Karine Ser-Le Roux Frédéric De Leeuw Corinne Laplace-Builhé Philippe Mauduit Edgardo D. Carosella Sébastien Banzet Jean-Jacques Lataillade Nathalie Rouas-Freiss Georges Uzan Juliette Peltzer Cord blood-endothelial colony forming cells are immunotolerated and participate at post-ischemic angiogenesis in an original dorsal chamber immunocompetent mouse model Stem Cell Research & Therapy Endothelial progenitor cells Cord blood-endothelial colony forming cells Immunotolerance Ischemia Angiogenesis |
| title | Cord blood-endothelial colony forming cells are immunotolerated and participate at post-ischemic angiogenesis in an original dorsal chamber immunocompetent mouse model |
| title_full | Cord blood-endothelial colony forming cells are immunotolerated and participate at post-ischemic angiogenesis in an original dorsal chamber immunocompetent mouse model |
| title_fullStr | Cord blood-endothelial colony forming cells are immunotolerated and participate at post-ischemic angiogenesis in an original dorsal chamber immunocompetent mouse model |
| title_full_unstemmed | Cord blood-endothelial colony forming cells are immunotolerated and participate at post-ischemic angiogenesis in an original dorsal chamber immunocompetent mouse model |
| title_short | Cord blood-endothelial colony forming cells are immunotolerated and participate at post-ischemic angiogenesis in an original dorsal chamber immunocompetent mouse model |
| title_sort | cord blood endothelial colony forming cells are immunotolerated and participate at post ischemic angiogenesis in an original dorsal chamber immunocompetent mouse model |
| topic | Endothelial progenitor cells Cord blood-endothelial colony forming cells Immunotolerance Ischemia Angiogenesis |
| url | http://link.springer.com/article/10.1186/s13287-020-01687-7 |
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