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

毛囊的形成是由于聚集的间充质（称为冷凝物）和表皮增厚（称为基板）之间的相互作用[1]。在发育过程中观察到的冷凝物成为成年毛囊中的毛乳头，就像冷凝物驱动毛囊发育一样，毛乳头是促进毛发生长的成年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。每一根头发都要经历生长、退化和再生的循环过程，以限制毛干的长度。这种循环受毛乳头的控制，并且在患有雄激素性脱发的毛囊中的每个毛发周期中，毛乳头中的间充质细胞的数量减少，导致毛干的进行性硬化和脱发的出现。目前的毛发移植只能采取不受雄激素性脱发影响的头发，并将其移植到受影响的区域。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增加头皮上的毛囊数量。因此，许多研究的重点一直是成人毛乳头，保留胚胎的“毛发诱导”的特点。当从毛囊中取出并放置在非毛囊上皮上时，毛乳头就像真皮冷凝物一样，可以诱导受体上皮中的毛囊从头生长[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，因此它诱导了一根头发，与目前的毛发移植技术相比不会产生任何改善。这不会导致毛囊总数的增加。毛乳头也可以从毛囊中分离出来，并在培养物中生长，导致其细胞数量增加，然而，这导致其诱导能力丧失，这与干扰的转录特征相对应[4]。我们先前证明，如果细胞在促进真皮球状体形成的悬滴中生长，则人毛乳头细胞的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，毛乳头细胞生长在三维球体可以诱导从头毛囊再生。使用植入培养的球状体来对抗脱发会导致毛囊数量的增加。

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.