Nanoscale microenvironment engineering based on layer-by-layer self-assembly to regulate hair follicle stem cell fate for regenerative medicine.
Nanoscale microenvironment engineering based on layer-by-layer self-assembly to regulate hair follicle stem cell fate for regenerative medicine.
复制标题
基于层层自组装的纳米微环境工程调控毛囊干细胞命运的再生医学
作者：
Chen P;Miao Y;Zhang F;Huang J;Chen Y;Fan Z;Yang L;Wang J;Hu Z
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（HFSC）和毛乳头细胞（DPC）移植到脱发区域。周期性毛发再生是由HFSC的周期性部分激活引起的。然而，以前的研究还没有成功地实现大规模的HFSC体外扩增，而不使用饲养细胞，缺乏研究集中在调控HFSC的命运毛囊（HF）再生。因此，再生医学中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并引导其命运用于组织再生的细胞微环境。研究方法：采用层层自组装技术将明胶和海藻酸钠包裹于HFSCs表面，构建HFSCs的仿生ECM，并将转化生长因子β 2（TGF-β 2）负载于包被层中，作为缓释信号分子，调控HFSCs的体内外命运。采用体外实验（细胞培养和siRNA）来研究所涉及的分子机制，并进行体内植入以评估毛发诱导效率。结果如下：为单个HFSC构建纳米级仿生ECM，其允许HFSC的稳定扩增并维持其干细胞特性。TGF-β 2加载到涂层中诱导CD34+干细胞转化为高度增殖的Lgr5+干细胞，类似于HF再生中HFSC的部分活化。因此，LbL包被和TGF-β 2负载分别在HF再生期间部分重建干细胞的静止和活化状态，从而模拟在HF循环期间调节干细胞命运以用于组织再生的微环境。当两种HFSC状态与新生小鼠真皮细胞共移植到裸鼠体内时，实现了改善的HF再生。结论：本研究为构建干细胞微环境和HF再生治疗脱发的实验模型提供了新的方法。
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 in vitro 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. Methods: 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 in vitro and in vivo. In vitro experiments (cell culture and siRNA) were employed to investigate the molecular mechanisms involved and in vivo implantation was carried out to evaluate hair induction efficiency. Results: 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. Conclusion: This study provides novel methods for the construction of stem cell microenvironments and experimental models of HF regeneration for the treatment of hair loss.
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影响因子：
11.4
作者：
Chacon-Martinez, Carlos Andres;Klose, Markus;Wickstroem, Sara A.
通讯作者：
Wickstroem, Sara A.
DOI：
10.1016/j.msec.2016.03.074
发表时间：
2017-01-01
影响因子：
7.9
作者：
Guo, Shanshan;Zhu, Xiaoying;Loh, Xian Jun
通讯作者：
Loh, Xian Jun
DOI：
10.1073/pnas.1309970110
发表时间：
2013-12-03
影响因子：
11.1
作者：
Higgins, Claire A.;Chen, James C.;Christiano, Angela M.
通讯作者：
Christiano, Angela M.
影响因子：
9.5
作者：
Li, Wenyan;Guan, Teng;Kong, Jiming
通讯作者：
Kong, Jiming
影响因子：
23.9
作者：
Genander, Maria;Cook, Peter J.;Ramskold, Daniel;Keyes, Brice E.;Mertz, Aaron F.;Sandberg, Rickard;Fuchs, Elaine
通讯作者：
Fuchs, Elaine