Current approaches fail at obtaining adequate functional human dermal papilla cells (DPCs) to regenerate hair follicles (HFs). Here we induce human dermal fibroblasts (hDFs) into hDPC-like cells (hDF-DPCs) through alginate-poly-L-lysine-alginate (APA) microencapsulation. Our results show that the derived hDF-DPCs are comparable to primary DPCs on the molecular level, and they can induce the formation of hair follicle-like structures and hair pigmentation in nude mice. RNA-seq analyses indicate the activation of Wnt signaling pathway during the hDF-DPCs conversion. Likewise, we demonstrate that mouse DFs differentiate into mouse DPC-like cells within the hydrogel microcapsules. The induction of dermal fibroblasts into DPC-like cells through biomimetic microencapsulation, devoid of chemical or gene reprogramming, would provide an alternative, abundant, and safe source of DPCs, which would help circumvent the bottleneck in DPC-based HF regeneration.

当前的方法不能获得足够的功能性人真皮乳头细胞（DPC）来再生毛囊（HF）。在这里，我们通过藻酸盐-聚-L诱导人类皮肤成纤维细胞（hDFs）进入hDPC样细胞（hDF-DPCs）-赖氨酸海藻酸盐（APA）微囊化。我们的结果表明，衍生的hDF-DPC在分子水平上可与初级DPC相提并论，它们可以诱导裸鼠毛囊样结构的形成和头发色素沉着。RNA序列分析表明在hDF-DPC转换过程中Wnt信号通路的激活。同样，我们证明了小鼠DFs在水凝胶微胶囊内分化为小鼠DPC样细胞。通过仿生微囊化将真皮成纤维细胞诱导成DPC样细胞，而无需化学或基因重编程，将提供DPC的替代，丰富且安全的来源，这将有助于绕开基于DPC的HF再生的瓶颈。