Fetal fibroblasts and keratinocytes with immunosuppressive properties for allogeneic cell-based wound therapy.
Fetal skin heals rapidly without scar formation early in gestation, conferring to fetal skin cells a high and unique potential for tissue regeneration and scar management. In this study, we investigated the possibility of using fetal fibroblasts and keratinocytes to stimulate wound repair and regene...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3722184?pdf=render |
| _version_ | 1811336647948632064 |
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| author | Thomas Zuliani Soraya Saiagh Anne-Chantal Knol Julie Esbelin Brigitte Dréno |
| author_facet | Thomas Zuliani Soraya Saiagh Anne-Chantal Knol Julie Esbelin Brigitte Dréno |
| author_sort | Thomas Zuliani |
| collection | DOAJ |
| description | Fetal skin heals rapidly without scar formation early in gestation, conferring to fetal skin cells a high and unique potential for tissue regeneration and scar management. In this study, we investigated the possibility of using fetal fibroblasts and keratinocytes to stimulate wound repair and regeneration for further allogeneic cell-based therapy development. From a single fetal skin sample, two clinical batches of keratinocytes and fibroblasts were manufactured and characterized. Tolerogenic properties of the fetal cells were investigated by allogeneic PBMC proliferation tests. In addition, the potential advantage of fibroblasts/keratinocytes co-application for wound healing stimulation has been examined in co-culture experiments with in vitro scratch assays and a multiplex cytokines array system. Based on keratin 14 and prolyl-4-hydroxylase expression analyses, purity of both clinical batches was found to be above 98% and neither melanocytes nor Langerhans cells could be detected. Both cell types demonstrated strong immunosuppressive properties as shown by the dramatic decrease in allogeneic PBMC proliferation when co-cultured with fibroblasts and/or keratinocytes. We further showed that the indoleamine 2,3 dioxygenase (IDO) activity is required for the immunoregulatory activity of fetal skin cells. Co-cultures experiments have also revealed that fibroblasts-keratinocytes interactions strongly enhanced fetal cells secretion of HGF, GM-CSF, IL-8 and to a lesser extent VEGF-A. Accordingly, in the in vitro scratch assays the fetal fibroblasts and keratinocytes co-culture accelerated the scratch closure compared to fibroblast or keratinocyte mono-cultures. In conclusion, our data suggest that the combination of fetal keratinocytes and fibroblasts could be of particular interest for the development of a new allogeneic skin substitute with immunomodulatory activity, acting as a reservoir for wound healing growth factors. |
| first_indexed | 2024-04-13T17:42:40Z |
| format | Article |
| id | doaj.art-a88eea3d938941219470c9e9bf38c484 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T17:42:40Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-a88eea3d938941219470c9e9bf38c4842022-12-22T02:37:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0187e7040810.1371/journal.pone.0070408Fetal fibroblasts and keratinocytes with immunosuppressive properties for allogeneic cell-based wound therapy.Thomas ZulianiSoraya SaiaghAnne-Chantal KnolJulie EsbelinBrigitte DrénoFetal skin heals rapidly without scar formation early in gestation, conferring to fetal skin cells a high and unique potential for tissue regeneration and scar management. In this study, we investigated the possibility of using fetal fibroblasts and keratinocytes to stimulate wound repair and regeneration for further allogeneic cell-based therapy development. From a single fetal skin sample, two clinical batches of keratinocytes and fibroblasts were manufactured and characterized. Tolerogenic properties of the fetal cells were investigated by allogeneic PBMC proliferation tests. In addition, the potential advantage of fibroblasts/keratinocytes co-application for wound healing stimulation has been examined in co-culture experiments with in vitro scratch assays and a multiplex cytokines array system. Based on keratin 14 and prolyl-4-hydroxylase expression analyses, purity of both clinical batches was found to be above 98% and neither melanocytes nor Langerhans cells could be detected. Both cell types demonstrated strong immunosuppressive properties as shown by the dramatic decrease in allogeneic PBMC proliferation when co-cultured with fibroblasts and/or keratinocytes. We further showed that the indoleamine 2,3 dioxygenase (IDO) activity is required for the immunoregulatory activity of fetal skin cells. Co-cultures experiments have also revealed that fibroblasts-keratinocytes interactions strongly enhanced fetal cells secretion of HGF, GM-CSF, IL-8 and to a lesser extent VEGF-A. Accordingly, in the in vitro scratch assays the fetal fibroblasts and keratinocytes co-culture accelerated the scratch closure compared to fibroblast or keratinocyte mono-cultures. In conclusion, our data suggest that the combination of fetal keratinocytes and fibroblasts could be of particular interest for the development of a new allogeneic skin substitute with immunomodulatory activity, acting as a reservoir for wound healing growth factors.http://europepmc.org/articles/PMC3722184?pdf=render |
| spellingShingle | Thomas Zuliani Soraya Saiagh Anne-Chantal Knol Julie Esbelin Brigitte Dréno Fetal fibroblasts and keratinocytes with immunosuppressive properties for allogeneic cell-based wound therapy. PLoS ONE |
| title | Fetal fibroblasts and keratinocytes with immunosuppressive properties for allogeneic cell-based wound therapy. |
| title_full | Fetal fibroblasts and keratinocytes with immunosuppressive properties for allogeneic cell-based wound therapy. |
| title_fullStr | Fetal fibroblasts and keratinocytes with immunosuppressive properties for allogeneic cell-based wound therapy. |
| title_full_unstemmed | Fetal fibroblasts and keratinocytes with immunosuppressive properties for allogeneic cell-based wound therapy. |
| title_short | Fetal fibroblasts and keratinocytes with immunosuppressive properties for allogeneic cell-based wound therapy. |
| title_sort | fetal fibroblasts and keratinocytes with immunosuppressive properties for allogeneic cell based wound therapy |
| url | http://europepmc.org/articles/PMC3722184?pdf=render |
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