间质细胞
自愈水凝胶
角膜上皮
细胞生物学
上皮
再生(生物学)
阿尔法(金融)
化学
材料科学
壳聚糖
组织工程
生物医学工程
角膜
生物
医学
病理
癌症研究
眼科
高分子化学
外科
生物化学
患者满意度
结构效度
作者
Qiaomei Tang,Chenqi Luo,Bing Lu,Qiang Fu,Houfa Yin,Zhenwei Qin,Danni Lyu,Lifang Zhang,Zhi Fang,Yanan Zhu,Ke Yao
标识
DOI:10.1016/j.actbio.2017.08.001
摘要
Corneal epithelium integrity depends on continuous self-renewing of epithelium and connections between adjacent cells or between the cells and the basement membrane. Self-renewing epithelium cells mainly arise from the continuous proliferation and differentiation of the basal layer and limbal stem cells. The aim of the present study was to generate a bioactive, thermosensitive chitosan–gelatin hydrogel (CHI hydrogel) by incorporating exogenous recombinant human stromal cell–derived factor-1 alpha (SDF-1 alpha) for corneal epithelium regeneration. The exogenous SDF-1 alpha could enhance the stem cells proliferation, chemotaxis and migration, and the expression levels of related genes were significantly elevated in LESCs and mesenchymal stem cells (MSCs) in vitro. Moreover, the MSCs promoted the proliferation and maintained the corneal fate of the LESCs. The rat alkali injury model was used for in vivo study. The injured eyes were covered with CHI hydrogel alone or rhSDF-1 alpha-loaded CHI hydrogel. All rats were followed for 13 days. Histological examination showed that the SDF-1 alpha/CHI hydrogel complex group had a nearly normal thickness; moreover, it was also found that this group could upregulate the expression of some genes and had more ΔNp63-positive cells. The SDF-1 alpha/CHI hydrogel complex group had a more tightly arranged epithelium compared with the control group using transmission electron microscopy (TEM). The mechanism for this may have involved the activation of stem cell homing and the secretion of growth factors via the SDF-1/CXCR4 chemokine axis. Therefore, SDF-1 alpha/CHI hydrogel complexes could provide a new idea for the clinical application. The clarity of cornea is important for normal vision. The loss or dysfunction of LESCs leads to the impairment of corneal epithelium. The complete regeneration of corneal epithelium has not been achieved. Our study demonstrated that the incorporation of rhSDF-1 alpha with CHI hydrogel accelerated corneal epithelium reconstruction with more native structural and functional properties. The mechanism may involve in inducing proliferation and migration of the LESCs and MSCs to the injury site via the SDF-1/CXCR4 chemokine axis. Therefore, SDF-1 alpha/CHI hydrogel complexes could be a practical application for clinical therapy.
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