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% O₂), physiological/normoxic (6% O₂), or hypoxic (1% O₂) 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 BMP4, LEF1, SOX2, and VCAN. In DSCs, both normoxia and hypoxia upregulated SOX2 expression, whereas hypoxia downregulated BMP4 expression. Microarray analysis revealed that normoxia increased the expression of pluripotency-related genes, including SPRY, NR0B1, MSX2, IFITM1, and DAZL, compared with hyperoxia. In an in vivo 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.

中文翻译：

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在生理氧条件下培养的人真皮鞘细胞的毛发再生潜力。

我们研究了氧张力对人真皮乳头细胞 (DPC) 和真皮鞘细胞 (DSC) 增殖和毛发诱导能力的影响。DPC 和 DSC 分别从人类毛囊中获得，并分别在大气/高氧 (20% O ₂ )、生理/常氧 (6% O ₂ ) 或缺氧 (1% O ₂ ) 条件下培养。在常氧条件下，DPC 和 DSC 的增殖最高。与高氧相比，低氧抑制了 DPCs 的增殖，但增强了 DSCs 的增殖。在 DPC 中，缺氧下调毛发诱导能力相关基因的表达，包括BMP4、LEF1、SOX2和VCAN. 在 DSC 中，常氧和缺氧都会上调SOX2 的表达，而缺氧会下调BMP4 的表达。微阵列分析显示，正常氧增加的多能性相关的基因，包括表达SPRY，NR0B1，MSX2，IFITM1，和DAZL，高氧进行比较。在体内毛囊重建实验，培养的 DPCs 和 DSCs 与新生小鼠表皮角质形成细胞一起使用腔室法移植到裸鼠体内。在该实验中，常氧导致 DPC 毛囊的最有效诱导，而缺氧导致 DSC 毛囊的最有效诱导和成熟。这些结果表明，将生理/缺氧氧张力应用于培养的人类 DSC 可增强皮肤工程和临床应用中毛发诱导性的增殖和维持。