title: Cell therapy for full-thickness wounds: are fetal dermal cells a potential source?
abstract: The application of autologous dermal fibroblasts has been shown to improve burn wound healing. However, a major hurdle is the availability of sufficient healthy skin as a cell source. We investigated fetal dermal cells as an alternative source for cell-based therapy for skin regeneration. Human (hFF), porcine fetal (pFF) or autologous dermal fibroblasts (AF) were seeded in a collagen-elastin substitute (Novomaix, NVM), which was applied in combination with an autologous split thickness skin graft (STSG) to evaluate the effects of these cells on wound healing in a porcine excisional wound model. Transplantation of wounds with NVM+hFF showed an increased influx of inflammatory cells (e.g., neutrophils, macrophages, CD4(+) and CD8(+) lymphocytes) compared to STSG, acellular NVM (Acell-NVM) and NVM+AF at post-surgery days 7 and/or 14. Wounds treated with NVM+pFF presented only an increase in CD8(+) lymphocyte influx. Furthermore, reduced alpha-smooth muscle actin (αSMA) expression in wound areas and reduced contraction of the wounds was observed with NVM+AF compared to Acell-NVM. Xenogeneic transplantation of NVM+hFF increased αSMA expression in wounds compared to NVM+AF. An improved scar quality was observed for wounds treated with NVM+AF compared to Acell-NVM, NVM+hFF and NVM+pFF at day 56. In conclusion, application of autologous fibroblasts improved the overall outcome of wound healing in comparison to fetal dermal cells and Acell-NVM, whereas application of fetal dermal fibroblasts in NVM did not improve wound healing of full-thickness wounds in a porcine model. Although human fetal dermal cells demonstrated an increased immune response, this did not seem to affect scar quality.
authors.affiliation: Department of Plastic, Reconstructive and Hand Surgery, Research Institute MOVE, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: J J
authors.initials: JJ
authors.lastname: Akershoek
authors.affiliation: Association of Dutch Burn Centres, Zeestraat 27-29, 1941 AJ, Beverwijk, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Vlig
authors.affiliation: Department of Plastic, Reconstructive and Hand Surgery, Research Institute MOVE, VU University Medical Center, Amsterdam, The Netherlands.|Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: W
authors.initials: W
authors.lastname: Talhout
authors.affiliation: Association of Dutch Burn Centres, Zeestraat 27-29, 1941 AJ, Beverwijk, The Netherlands.
authors.forename: B K H L
authors.initials: BK
authors.lastname: Boekema
authors.affiliation: Euro Tissue Bank, Beverwijk, The Netherlands.
authors.forename: C D
authors.initials: CD
authors.lastname: Richters
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: R H J
authors.initials: RH
authors.lastname: Beelen
authors.affiliation: Department of Plastic, Reconstructive and Hand Surgery, Research Institute MOVE, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: K M
authors.initials: KM
authors.lastname: Brouwer
authors.affiliation: Department of Plastic, Reconstructive and Hand Surgery, Research Institute MOVE, VU University Medical Center, Amsterdam, The Netherlands.|Association of Dutch Burn Centres, Zeestraat 27-29, 1941 AJ, Beverwijk, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Middelkoop
authors.affiliation: Association of Dutch Burn Centres, Zeestraat 27-29, 1941 AJ, Beverwijk, The Netherlands. mulrich@burns.nl.|Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands. mulrich@burns.nl.
authors.forename: M M W
authors.initials: MM
authors.lastname: Ulrich
mesh_terms: D000818:Animals; D017690:Cell Transplantation / Q000379:methods*; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002478:Cells, Cultured; D020405:Dermis / Q000637:transplantation*; D004195:Disease Models, Animal; D005333:Fetus; D064593:Heterografts; D006801:Humans; D013552:Swine; D014947:Wounds and Injuries / Q000473:pathology / Q000628:therapy*
keywords: Allogeneic/xenogeneic transplantation; Dermal substitutes; Fetal fibroblasts; Full-thickness wounds; Mesenchymal stem cells