Nolte Sonja Veronika, Xu Weiguo, Rennekampff Hans-Oliver, Rodemann H Peter
Section of Burn Surgery and Skin Regeneration, BG Trauma Center, Tuebingen, Germany.
Cells Tissues Organs. 2008;187(3):165-76. doi: 10.1159/000111805. Epub 2007 Nov 28.
Enormous advances in the development of skin substitutes have occurred in the past 3 decades. Major obstacles yet to be overcome in the quest for an optimal skin substitute include controlling scar formation, contraction and the loss of adnexal structures. Mesenchyme-derived signals are essential for epithelial proliferation, skin morphogenesis, homeostasis and differentiation. Having previously shown that fibroblasts differentiate along a lineage from highly proliferative progenitor fibroblasts with characteristic spindle-shaped appearance to differentiated postmitotic polygonal fibrocytes, we have now established that the different subsets of fibroblasts exert significantly different patterns of cytokine release and that the highest levels of keratinocyte growth factor and transforming growth factor-beta1 expression result from differentiated fibroblasts. Coculture studies with keratinocytes reveal that postmitotic fibroblasts stimulate keratinocyte proliferation to a greater extent than progenitor fibroblasts. Acellular and fibroblast-seeded dermal substitutes have been shown to improve scarring and contraction in animal studies, the latter substitutes yielding the most favorable results. Fibroblasts from different body sites display different functional properties which may affect their suitability for dermal substitutes. Future in vivo human studies in tissue-engineered dermal substitutes will likely focus on fibroblast-seeded lattices and the impact of fibroblast subpopulations and bone marrow-derived mesenchymal stem cells on dermal regeneration.
在过去30年里，皮肤替代物的研发取得了巨大进展。在寻求理想皮肤替代物的过程中，仍有待克服的主要障碍包括控制瘢痕形成、挛缩以及附属器结构的丧失。间充质衍生信号对于上皮细胞增殖、皮肤形态发生、内环境稳定和分化至关重要。此前我们已表明，成纤维细胞会沿着一条谱系从具有特征性纺锤形外观的高增殖祖细胞成纤维细胞分化为分化后的有丝分裂后多边形纤维细胞，现在我们确定，不同亚群的成纤维细胞释放细胞因子的模式显著不同，且角质形成细胞生长因子和转化生长因子-β1的最高表达水平来自分化后的成纤维细胞。与角质形成细胞的共培养研究表明，有丝分裂后成纤维细胞比祖细胞成纤维细胞更能刺激角质形成细胞增殖。在动物研究中，脱细胞和接种了成纤维细胞的真皮替代物已被证明可改善瘢痕形成和挛缩，后者产生的效果最为理想。来自不同身体部位的成纤维细胞具有不同的功能特性，这可能会影响它们用于真皮替代物的适用性。未来在组织工程真皮替代物方面的人体体内研究可能会集中在接种了成纤维细胞的支架以及成纤维细胞亚群和骨髓来源的间充质干细胞对真皮再生的影响上。
