Abreu Carla M, Pirraco Rogério P, Reis Rui L, Cerqueira Mariana T, Marques Alexandra P
3B's Research Group - Biomaterials, Biodegradables and Biomimetics, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, University of Minho, Guimarães, Portugal.
ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
Stem Cell Res Ther. 2021 Jan 15;12(1):62. doi: 10.1186/s13287-020-02104-9.
Hair follicle (HF) development and growth are dependent on epithelial-mesenchymal interactions (EMIs). Dermal papilla (DP) cells are recognized as the key inductive mesenchymal player, but the ideal source of receptive keratinocytes for human HF regeneration is yet to be defined. We herein investigated whether human interfollicular epidermal keratinocytes with stem-like features (EpSlKCs), characterized by a α6/CD71 expression, can replace human hair follicular keratinocytes (HHFKCs) for the recreation of the HF epithelium and respective EMIs.
The α6/CD71 cellular fraction was selected from the whole interfollicular keratinocyte population through fluorescence-activated cell sorting and directly compared with follicular keratinocytes in terms of their proliferative capacity and phenotype. The crosstalk with DP cells was studied in an indirect co-culture system, and EpSlKC hair forming capacity tested in a hair reconstitution assay when combined with DP cells.
EpSlKCs exhibited a phenotypic profile similar to follicular keratinocytes and were capable of increasing DP cell proliferation and, for short co-culture times, the number of alkaline phosphatase-active cells, suggesting an improvement of their inductivity. Moreover, the recreation of immature HFs and sebaceous glands was observed after EpSlKC and DP cell co-grafting in nude mice.
Our results suggest that EpSlKCs are akin to follicular keratinocytes and can crosstalk with DP cells, contributing to HF morphogenesis in vivo, thus representing an attractive epithelial cell source for hair regeneration strategies.
毛囊（HF）的发育和生长依赖于上皮-间充质相互作用（EMIs）。真皮乳头（DP）细胞被认为是关键的诱导性间充质细胞，但用于人类HF再生的理想的角质形成细胞来源尚未确定。我们在此研究了具有干细胞样特征（EpSlKCs）的人类毛囊间表皮角质形成细胞，其特征为α6/CD71表达，是否可以替代人类毛囊角质形成细胞（HHFKCs）来重建HF上皮和相应的EMIs。
通过荧光激活细胞分选从整个毛囊间角质形成细胞群体中筛选出α6/CD71细胞亚群，并在增殖能力和表型方面与毛囊角质形成细胞直接比较。在间接共培养系统中研究与DP细胞的相互作用，并在与DP细胞联合时通过毛发重建试验测试EpSlKC的毛发形成能力。
EpSlKCs表现出与毛囊角质形成细胞相似的表型特征，能够增加DP细胞的增殖，并且在短时间共培养时，增加碱性磷酸酶活性细胞的数量，表明其诱导能力有所提高。此外，在裸鼠中EpSlKC和DP细胞共同移植后观察到未成熟HF和皮脂腺的重建。
我们的结果表明，EpSlKCs类似于毛囊角质形成细胞，能够与DP细胞相互作用，在体内促进HF形态发生，因此是毛发再生策略中一种有吸引力的上皮细胞来源。
