Hair Regeneration Potential of Human Dermal Sheath Cells Cultured Under Physiological Oxygen
Hair Regeneration Potential of Human Dermal Sheath Cells Cultured Under Physiological Oxygen
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DOI：
10.1089/ten.tea.2019.0329
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发表时间：
2020-06-26
影响因子：
4.1
通讯作者：
Yoshimura, Kotaro
中科院分区：
文献类型：
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作者：
Kanayama, Koji;Takada, Hitomi;Yoshimura, Kotaro
研究了氧分压对人毛乳头细胞（DPC）和真皮鞘细胞（DSCs）增殖和毛发诱导能力的影响。DPC和DSC分别从人毛囊中获得，并分别在大气/高氧（20%O-2）、生理/常氧（6%O-2）或低氧（1%O-2）条件下培养。在常氧条件下，毛乳头细胞和毛乳头干细胞的增殖最快。与高氧相比，低氧抑制了DPCs的增殖，但促进了DSCs的增殖。在毛原细胞中，缺氧下调了毛发诱导能力相关基因的表达，包括BMP 4、LEF 1、SOX 2和VCAN。常氧和低氧均能上调DSCs中SOX 2的表达，而低氧则下调BMP 4的表达。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SPRY、NR 0 B1、MSX 2、IFITM 1和DAZL。在体外毛囊重建实验中，采用小室法将培养的毛原细胞和毛干细胞与新生小鼠表皮角质形成细胞移植到裸鼠体内。在该实验中，常氧导致DPC毛囊的最有效的诱导，而缺氧导致DSC毛囊的最有效的诱导和成熟。这些结果表明，应用生理/缺氧氧张力培养的人DSC增强增殖和维持头发诱导皮肤工程和临床应用。真皮鞘细胞（DSCs）和真皮乳头细胞（DPC）是基于细胞的再生治疗的有用细胞来源。这是第一份描述低氧条件对DSC更好的报告。DSCs的常氧和低氧培养有利于扩增这些毛囊细胞，并促进伤口愈合和毛发再生的基于细胞的治疗的发展。目前的研究支持优化的氧分压可以应用于将扩增的人DPC和DSC用于皮肤工程和临床应用。
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-2), physiological/normoxic (6% O-2), or hypoxic (1% O-2) 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, includingBMP4,LEF1,SOX2, andVCAN. In DSCs, both normoxia and hypoxia upregulatedSOX2expression, whereas hypoxia downregulatedBMP4expression. Microarray analysis revealed that normoxia increased the expression of pluripotency-related genes, includingSPRY,NR0B1,MSX2,IFITM1, andDAZL, compared with hyperoxia. In anin vivohair 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.