Department of Plastic and Aesthetic Surgery, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, Guangdong 510515, China.
Theranostics. 2020 Sep 22;10(25):11673-11689. doi: 10.7150/thno.48723. eCollection 2020.
Hair regenerative medicine, a promising strategy for the treatment of hair loss, will likely involve the transplantation of autologous hair follicular stem cells (HFSCs) and dermal papilla cells (DPCs) into regions of hair loss. Cyclic hair regeneration results from the periodic partial activation of HFSCs. However, previous studies have not successfully achieved large-scale HFSC expansion without the use of feeder cells with a lack of research focused on regulating HFSC fate for hair follicular (HF) regeneration. Hence, an emerging focus in regenerative medicine is the reconstruction of natural extracellular matrix (ECM) regulatory characteristics using biomaterials to generate cellular microenvironments for expanding stem cells and directing their fate for tissue regeneration. HFSCs were coated with gelatin and alginate using layer-by-layer (LbL) self-assembly technology to construct biomimetic ECM for HFSCs; after which transforming growth factor (TGF)-β2 was loaded into the coating layer, which served as a sustained-release signal molecule to regulate the fate of HFSCs both and . experiments (cell culture and siRNA) were employed to investigate the molecular mechanisms involved and implantation was carried out to evaluate hair induction efficiency. Nanoscale biomimetic ECM was constructed for individual HFSCs, which allowed for the stable amplification of HFSCs and maintenance of their stem cell properties. TGF-β2 loading into the coating layer induced transformation of CD34 stem cells into highly proliferating Lgr5 stem cells, similar to the partial activation of HFSCs in HF regeneration. Thus, LbL coating and TGF-β2 loading partially reconstructed the quiescent and activated states, respectively, of stem cells during HF regeneration, thereby mimicking the microenvironment that regulates stem cell fate for tissue regeneration during HF cycling. Improved HF regeneration was achieved when the two HFSC states were co-transplanted with neonatal mouse dermal cells into nude mice. This study provides novel methods for the construction of stem cell microenvironments and experimental models of HF regeneration for the treatment of hair loss.
毛发再生医学是治疗脱发的一种有前途的策略，可能涉及将自体毛囊干细胞 (HFSCs) 和真皮乳头细胞 (DPCs) 移植到脱发区域。周期性的毛发再生源于 HFSCs 的周期性部分激活。然而，以前的研究未能在不使用饲养细胞的情况下成功地实现 HFSC 的大规模扩增，也缺乏对调节 HFSC 命运以促进毛囊 (HF) 再生的研究。因此，再生医学的一个新兴焦点是使用生物材料重建天然细胞外基质 (ECM) 调节特性，以产生用于扩增干细胞的细胞微环境，并指导其用于组织再生的命运。使用层层自组装 (LbL) 技术将 HFSCs 用明胶和海藻酸钠包被，构建用于 HFSCs 的仿生 ECM；然后将转化生长因子 (TGF)-β2 载入涂层中，作为一种持续释放的信号分子，调节 HFSCs 的命运。通过细胞培养和 siRNA 实验研究了所涉及的分子机制，并进行了植入实验以评估毛发诱导效率。构建了纳米级仿生 ECM 用于单个 HFSCs，实现了 HFSCs 的稳定扩增和干细胞特性的维持。TGF-β2 载入涂层诱导 CD34 干细胞转化为高增殖的 Lgr5 干细胞，类似于 HF 再生过程中 HFSCs 的部分激活。因此，LbL 涂层和 TGF-β2 载入分别部分重建了 HF 再生过程中干细胞的静止和激活状态，从而模拟了调节 HF 循环期间干细胞命运的组织再生微环境。当将两种 HFSC 状态与新生小鼠真皮细胞共移植到裸鼠中时，HF 得到了更好的再生。本研究为构建干细胞微环境和 HF 再生实验模型提供了新方法，可用于治疗脱发。
