Understanding of the use of dermal papilla cells as a cell therapy for hair regeneration

毛囊的形成是簇状间充质(称为凝集物)和表皮增厚(称为胎盘)相互作用的结果。发育过程中观察到的凝结物成为成人毛囊中的毛乳头，就像凝结物推动毛囊发育一样，毛乳头是促进毛发生长的成人毛囊的关键组成部分[2]。毛囊也是一个重要的模型系统，因为它是一个自然再生的器官结构。每一根头发都会经历一个生长、退化和再生的循环过程，以限制发干的长度。这种循环是在毛乳头的控制下进行的，在患有雄激素性脱发的毛囊的每个毛发周期中，毛乳头中的间充质细胞数量减少，导致毛干逐渐缩小，出现脱发。目前的头发移植只能将未受雄激素性脱发影响的头发移植到受影响的部位。虽然美容效果是有帮助的，但患者在手术后仍然有相同的数字。目前，还没有商业系统可以使头皮上的毛囊数量成倍增加。因此，很多研究焦点都集中在成人毛乳头上，这种毛乳头保留了胚胎诱导毛发的特征。当从毛囊中取出并放置在非毛囊上皮时，毛乳头就像真皮冷凝物一样，可以诱导受体毛囊上皮中的新生毛囊生长[3]。然而，作为脱发的一种策略，从毛囊中取出单个毛乳头并将其移植到诱导出单个毛发，并不会比目前的毛发移植技术有任何改进。这不会导致毛囊总数增加。毛乳头也可以从毛囊中分离出来并在培养中生长，导致它们的细胞数量增加，然而，这会导致它们的诱导能力丧失，对应于转录信号的扰动[4]。我们以前曾证明，如果人毛乳头细胞生长在促进真皮球体形成的悬滴中，其转录特征和诱导能力可以部分恢复[4]。因此，作为一种细胞治疗策略，生长在三维球体中的毛乳头细胞可以诱导新生毛囊再生。使用植入培养的球体来对抗脱发将导致毛囊数量增加。

Hair follicles develop as a result of reciprocal interactions [1] between clustered mesenchyme known as the condensate, and an epidermal thickening known as a placode. The condensate observed during development becomes the dermal papilla in the adult hair follicle, and just as the condensate drives hair follicle development, the dermal papilla is a key component of the adult follicle that promotes hair growth [2]. The hair follicle is also an important model system as it is a naturally regenerating organ structure. Every individual hair goes through a cycling process of growth, degeneration and regeneration in order to limit the length of the hair shaft. This cycling is under control of the dermal papilla and in each hair cycle in follicles suffering from androgenic alopecia, the number of mesenchymal cells in the dermal papilla is reduced resulting in a progressive miniaturisation of the hair shaft and the appearance of hair loss. Current hair transplantation can only take hairs that are not affected by androgenic alopecia and transplant them into affected areas. Although the cosmetic effect is helpful, the patient still has the same number after the procedure. Currently, there are no commercial systems which work to multiply the number of follicles on the scalp. As such, a lot of research focus has been on the adult dermal papilla which retains embryonic 'hair inducing' characteristics. When removed from the hair follicle and placed against non-follicular epithelium, the dermal papilla acts like a dermal condensate, and can induce de novo hair follicle growth in recipient epithelium [3]. However, as a strategy for hair loss, taking a single dermal papilla from a hair follicle and transplanting it so it induces a single hair, does not result in any improvement over current hair transplantation techniques. This does not result in an increase in overall hair follicle numbers. Dermal papilla can also be isolated from follicles and grown in culture resulting in an increase in their cell number, however, this results in a loss of their inductive capacity corresponding with a perturbed transcriptional signature [4]. We previously demonstrated that the transcriptional signature and inductive capacity of human dermal papilla cells could be partially restored, if the cells were grown in hanging drops promoting the formation of dermal spheroids [4]. Thus, as a cell therapy strategy, dermal papilla cells grown in 3D spheroids can induce de novo follicle regeneration. Using implanted cultured spheroids to combat hair loss would result in an increased number of hair follicles.