Akershoek J J, Vlig M, Talhout W, Boekema B K H L, Richters C D, Beelen R H J, Brouwer K M, Middelkoop E, Ulrich M M W
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.
Cell Tissue Res. 2016 Apr;364(1):83-94. doi: 10.1007/s00441-015-2293-6. Epub 2015 Oct 9.
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.
自体真皮成纤维细胞的应用已被证明可促进烧伤创面愈合。然而,一个主要障碍是缺乏足够的健康皮肤作为细胞来源。我们研究了胎儿真皮细胞作为基于细胞的皮肤再生治疗的替代来源。将人胎儿成纤维细胞(hFF)、猪胎儿成纤维细胞(pFF)或自体真皮成纤维细胞(AF)接种于胶原-弹性蛋白替代物(Novomaix,NVM)中,并将其与自体中厚皮片(STSG)联合应用,以评估这些细胞对猪切除创面模型伤口愈合的影响。与STSG、无细胞NVM(Acell-NVM)和NVM+AF相比,在术后第7天和/或第14天,用NVM+hFF处理的伤口显示炎症细胞(如中性粒细胞、巨噬细胞、CD4(+)和CD8(+)淋巴细胞)的流入增加。用NVM+pFF处理的伤口仅显示CD8(+)淋巴细胞流入增加。此外,与Acell-NVM相比,NVM+AF处理的伤口区域α-平滑肌肌动蛋白(αSMA)表达降低,伤口收缩减少。与NVM+AF相比,NVM+hFF的异种移植增加了伤口中αSMA的表达。在第56天时,与Acell-NVM、NVM+hFF和NVM+pFF相比,用NVM+AF处理的伤口瘢痕质量得到改善。总之,与胎儿真皮细胞和Acell-NVM相比,自体成纤维细胞的应用改善了伤口愈合的总体结果,而在NVM中应用胎儿真皮成纤维细胞并未改善猪模型中全层伤口的愈合。尽管人胎儿真皮细胞表现出免疫反应增加,但这似乎并未影响瘢痕质量。