Zhou Linli, Yang Kun, Xu Mingang, Andl Thomas, Millar Sarah E, Boyce Steven, Zhang Yuhang
Division of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, OH, USA.
Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, PA, USA.
FEBS J. 2016 Aug;283(15):2823-35. doi: 10.1111/febs.13784. Epub 2016 Jul 11.
Bioengineering hair follicles using cells isolated from human tissue remains a difficult task. Dermal papilla (DP) cells are known to guide the growth and cycling activities of hair follicles by interacting with keratinocytes. However, DP cells quickly lose their inductivity during in vitro passaging. Rodent DP cell cultures need external addition of growth factors, including WNT and BMP molecules, to maintain the hair inductive property. CD133 is expressed by a subpopulation of DP cells that are capable of inducing hair follicle formation in vivo. We report here that expression of a stabilized form of β-catenin promoted clonal growth of CD133-positive (CD133+) DP cells in in vitro three-dimensional hydrogel culture while maintaining expression of DP markers, including alkaline phosphatase (AP), CD133, and integrin α8. After a 2-week in vitro culture, cultured CD133+ DP cells with up-regulated β-catenin activity led to an accelerated in vivo hair growth in reconstituted skin compared to control cells. Further analysis showed that matrix cell proliferation and differentiation were significantly promoted in hair follicles when β-catenin signaling was up-regulated in CD133+ DP cells. Our data highlight an important role for β-catenin signaling in promoting the inductive capability of CD133+ DP cells for in vitro expansion and in vivo hair follicle regeneration, which could potentially be applied to cultured human DP cells.
利用从人体组织分离出的细胞进行生物工程毛囊仍然是一项艰巨的任务。已知真皮乳头（DP）细胞通过与角质形成细胞相互作用来引导毛囊的生长和循环活动。然而，DP细胞在体外传代过程中会迅速失去其诱导能力。啮齿动物DP细胞培养需要外部添加生长因子，包括WNT和BMP分子，以维持毛发诱导特性。CD133由DP细胞的一个亚群表达，该亚群能够在体内诱导毛囊形成。我们在此报告，稳定形式的β-连环蛋白的表达促进了CD133阳性（CD133+）DP细胞在体外三维水凝胶培养中的克隆生长，同时维持了DP标志物的表达，包括碱性磷酸酶（AP）、CD133和整合素α8。经过2周的体外培养，与对照细胞相比，β-连环蛋白活性上调的培养CD133+ DP细胞导致重组皮肤中体内毛发生长加速。进一步分析表明，当CD133+ DP细胞中β-连环蛋白信号上调时，毛囊中的基质细胞增殖和分化显著促进。我们的数据突出了β-连环蛋白信号在促进CD133+ DP细胞的诱导能力以进行体外扩增和体内毛囊再生中的重要作用，这可能潜在地应用于培养的人DP细胞。
