Gharzi A, Reynolds A J, Jahoda C A B
School of Biological and Biomedical Sciences, South Road, University of Durham, UK.
Exp Dermatol. 2003 Apr;12(2):126-36. doi: 10.1034/j.1600-0625.2003.00106.x.
The capacity of adult hair follicle dermal cells to participate in new follicle induction and regeneration, and to elicit responses from diverse epithelial partners, demonstrates a level of developmental promiscuity and influence far exceeding that of interfollicular fibroblasts. We have recently suggested that adult follicle dermal cells have extensive stem or progenitor cell activities, including an important role in skin dermal wound healing. Given that up to now tissue engineered skin equivalents have several deficiencies, including the absence of hair follicles, we investigated the capacity of follicle dermal cells to be incorporated into skin wounds; to form hair follicles in wound environments; and to create a hair follicle-derived skin equivalent. In our study, we implanted rat follicle dermal cells labelled with a vital dye into ear and body skin wounds. We found that they were incorporated into the new dermis in a manner similar to skin fibroblasts, but that lower follicle dermal sheath also assimilated into hair follicles. Using different combinations of follicle dermal cells and outer root sheath epithelial cells in punch biopsy wounds, we showed that new hair follicles were formed only with the inclusion of intact dermal papillae. Finally by combining follicle dermal sheath and outer root sheath cells in organotypic chambers, we created a skin equivalent with characteristic dermal and epidermal architecture and a normal basement membrane - the first skin to be produced entirely from hair follicle cells. These data support the hypothesis that follicle dermal cells may be important in wound healing and demonstrate their potential usefulness in human skin equivalents and skin substitutes. While we have made progress towards producing skin equivalents that contain follicles, we suggest that the failure of cultured dermal papilla cells to induce follicle formation in wounds illustrates the complex role the follicle dermis may play in skin. We believe that it demonstrates a genuine dichotomy of activity for follicle cells within skin.
成年毛囊真皮细胞参与新毛囊诱导和再生,并引发来自不同上皮伙伴的反应的能力,表明其发育的混杂程度和影响力远超毛囊间成纤维细胞。我们最近提出,成年毛囊真皮细胞具有广泛的干细胞或祖细胞活性,包括在皮肤真皮伤口愈合中发挥重要作用。鉴于到目前为止组织工程皮肤替代物存在一些缺陷,包括没有毛囊,我们研究了毛囊真皮细胞整合到皮肤伤口中的能力;在伤口环境中形成毛囊的能力;以及创建毛囊来源的皮肤替代物的能力。在我们的研究中,我们将用活性染料标记的大鼠毛囊真皮细胞植入耳部和身体皮肤伤口。我们发现它们以类似于皮肤成纤维细胞的方式整合到新真皮中,但较低的毛囊真皮鞘也会融入毛囊。在打孔活检伤口中使用不同组合的毛囊真皮细胞和外根鞘上皮细胞,我们发现只有包含完整的真皮乳头才能形成新的毛囊。最后,通过在器官型培养室中组合毛囊真皮鞘和外根鞘细胞,我们创建了一种具有特征性真皮和表皮结构以及正常基底膜的皮肤替代物——第一种完全由毛囊细胞产生的皮肤。这些数据支持了毛囊真皮细胞在伤口愈合中可能很重要的假设,并证明了它们在人类皮肤替代物和皮肤替代品中的潜在用途。虽然我们在生产含有毛囊的皮肤替代物方面取得了进展,但我们认为培养的真皮乳头细胞未能在伤口中诱导毛囊形成,这说明了毛囊真皮在皮肤中可能发挥的复杂作用。我们认为这表明了皮肤内毛囊细胞活动的真正二分法。