Effects of Exosomes Derived from Dermal Papilla Cells on Hair Follicle Stem Cells and Hair Follicle Organoids

Effects of Exosomes Derived from Dermal Papilla Cells on Hair Follicle Stem Cells and Hair Follicle Organoids
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真皮乳头细胞来源的外泌体对毛囊干细胞和毛囊类器官的影响

DOI:
10.11232/aatex.27.1
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发表时间:
2022
期刊:
Alternatives to Animal Testing and Experimentation
影响因子:
--
通讯作者:
Fukuda Junji
Fukuda Junji
中科院分区:
--
文献类型:
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作者:
Zhou Yinghui;Yamane Monami;Suzuki Kohei;Nanmo Ayaka;Tu Shan;Kageyama Tatsuto;Fukuda Junji

文献摘要

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毛囊的发育和周期是由上皮细胞和间充质细胞之间的相互作用来调节的。负责调节的机制主要使用实验动物如啮齿动物胎儿进行研究。本研究的目的是通过使用人毛囊衍生细胞的体外细胞培养模型来了解这种通信。使用二维(2D)、球状体(3D)和球状体微孔阵列培养物在透氧基质(3D-oxy)中培养人毛乳头细胞(DPC)。收集并纯化培养基中分泌的外来体。所有三种类型的外泌体都适度促进了人毛囊干细胞(HFSC)的增殖。与来自其他两种培养方法的外泌体相比,来自3D-氧基培养物的外泌体最有效地上调HFSC中CD 200、CD 34和K15的表达。为了研究外泌体对体外毛囊形成的影响,使用小鼠胚胎上皮细胞和间充质细胞制备毛囊类器官。对促生发基因和HFSC标记基因的表达分析表明,来自3D-氧培养物的外泌体在体外维持干细胞和刺激毛囊发芽方面是最有效的。来自人DPC的外来体可能具有治疗脱发患者的巨大潜力。
Hair follicle development and cycle are regulated by the reciprocal interactions between epithelial and mesenchymal cells. Mechanisms responsible for the regulation have mainly been studied using experimental animals such as rodent fetuses. The purpose of this study is to understand such communications by using in vitro cell culture models of human hair follicle-derived cells. Human dermal papilla cells (DPCs) were cultured using 2-dimensional (2D), spheroid (3D), and spheroid microwell array cultures in an oxygen-permeable substrate (3D-oxy). Exosomes secreted in the culture media were collected and purified. All three types of exosomes moderately promoted proliferation of human hair follicle stem cells (HFSCs). Exosomes from the 3D-oxy culture most efficiently upregulated the expression of CD200, CD34, and K15 in HFSCs compared to those from the other two culture methods. To investigate the effects of exosomes on in vitro hair follicle formation, mouse embryonic epithelial and mesenchymal cells were used to prepare hair follicle organoids. The expression analysis of trichogenic and HFSC marker genes revealed that exosomes from the 3D-oxy culture were the most effective in maintaining stem cells and stimulating hair follicle sprouting in vitro. Exosomes from human DPCs may have substantial potential for treating patients with hair loss.