Department of Plastic Surgery, Jichi Medical University, Shimotsuke City, Japan.
Department of Plastic Surgery, The University of Tokyo School of Medicine, Tokyo, Japan.
Tissue Eng Part A. 2020 Nov;26(21-22):1147-1157. doi: 10.1089/ten.TEA.2019.0329. Epub 2020 Jun 26.
We investigated the effect of oxygen tension on the proliferation and hair-inductive capacity of human dermal papilla cells (DPCs) and dermal sheath cells (DSCs). DPCs and DSCs were separately obtained from human hair follicles and each cultured under atmospheric/hyperoxic (20% O), physiological/normoxic (6% O), or hypoxic (1% O) conditions. Proliferation of DPCs and DSCs was highest under normoxia. Compared with hyperoxia, hypoxia inhibited proliferation of DPCs, but enhanced that of DSCs. In DPCs, hypoxia downregulated the expression of hair-inductive capacity-related genes, including , , , and . In DSCs, both normoxia and hypoxia upregulated expression, whereas hypoxia downregulated expression. Microarray analysis revealed that normoxia increased the expression of pluripotency-related genes, including , , , , and , compared with hyperoxia. In an hair follicle reconstitution assay, cultured DPCs and DSCs were transplanted with newborn mouse epidermal keratinocytes into nude mice using a chamber method. In this experiment, normoxia resulted in the most efficient induction of DPC hair follicles, whereas hypoxia caused the most efficient induction and maturation of DSC hair follicles. These results suggest that application of physiological/hypoxic oxygen tension to cultured human DSCs enhances proliferation and maintenance of hair inductivity for skin engineering and clinical applications. Impact statement Dermal sheath cells (DSCs) and dermal papilla cells (DPCs) are useful cell sources for cell-based regenerative therapy. This is the first report to describe that low-oxygen conditions are better for DSCs. Normoxic and hypoxic culture of DSCs is beneficial for expanding these hair follicular cells and advancing development of cell-based therapy for both wound healing and hair regeneration. The current study supports that optimized oxygen tension can be applied to use expanded human DPCs and DSCs for skin engineering and clinical applications.
我们研究了氧张力对人真皮乳头细胞（DPCs）和真皮鞘细胞（DSCs）增殖和毛发生成能力的影响。将 DPCs 和 DSCs 分别从人毛囊中分离出来，在大气/高氧（20% O）、生理/常氧（6% O）或低氧（1% O）条件下培养。DPCs 和 DSCs 的增殖在常氧下最高。与高氧相比，低氧抑制 DPCs 的增殖，但增强 DSCs 的增殖。在 DPCs 中，低氧下调了毛发生成能力相关基因的表达，包括 、 、 、 。在 DSCs 中，常氧和低氧均上调 表达，而低氧下调 表达。微阵列分析显示，与高氧相比，常氧增加了多能性相关基因的表达，包括 、 、 、 和 。在毛囊重建实验中，采用腔室法将培养的 DPCs 和 DSCs 与新生小鼠表皮角质形成细胞共移植到裸鼠体内。在这个实验中，常氧导致 DPC 毛囊的诱导最有效，而低氧导致 DSC 毛囊的诱导和成熟最有效。这些结果表明，在培养的人 DSCs 中应用生理/低氧氧张力可增强毛囊诱导的增殖和维持，为皮肤工程和临床应用提供了依据。
