Corneal repair by human corneal keratocyte-reprogrammed iPSCs and amphiphatic carboxymethyl-hexanoyl chitosan hydrogel
Corneal repair by human corneal keratocyte-reprogrammed iPSCs and amphiphatic carboxymethyl-hexanoyl chitosan hydrogel
复制标题
DOI：
10.1016/j.biomaterials.2012.07.029
复制
发表时间：
2012-11-01
期刊：
影响因子：
14
通讯作者：
Chiou, Shih-Hwa
中科院分区：
文献类型：
--
作者：
Chien, Yueh;Liao, Yi-Wen;Chiou, Shih-Hwa
诱导多能干细胞(IPSCs)在再生医学中具有广阔的应用前景，但IPSCs能否促进角膜重建尚不清楚。在这项研究中，我们成功地将人角膜基质细胞重新编程为IPSCs。为了防止饲养层细胞的污染，将这些IPSCs培养到无血清和无饲养层的系统中，在该系统中，它们在30代中保持稳定，并显示出ESC样的多能性。为了探讨IPSCs作为生物工程替代物用于角膜修复的可行性，我们研制了一种热凝胶注射两亲性羧甲基己酰壳聚糖(CHC)纳米水凝胶，发现这种凝胶在培养液中可以提高IPSCs的存活率和CD44+比例，并保持其干细胞样基因的表达。IPSC和CHC水凝胶(IPSC/CHC水凝胶)联合治疗可促进角膜外科磨损损伤的创面愈合。在碱诱导的严重角膜损伤中，IPSC/CHC水凝胶通过下调氧化应激和招募内源性上皮细胞来恢复角膜上皮厚度，从而促进角膜重建。因此，我们证明，当这些人角膜细胞重编程的IPSCs与CHC水凝胶结合时，可以作为一种快速输送系统来有效地促进角膜伤口的愈合。此外，从角膜手术残留物中重新编程的IPSCs可以作为个性化治疗人类角膜损伤的替代细胞来源。(C)2012爱思唯尔有限公司。保留所有权利。
Induced pluripotent stem cells (iPSCs) have promising potential in regenerative medicine, but whether iPSCs can promote corneal reconstruction remains undetermined. In this study, we successfully reprogrammed human corneal keratocytes into iPSCs. To prevent feeder cell contamination, these iPSCs were cultured onto a serum- and feeder-free system in which they remained stable through 30 passages and showed ESC-like pluripotent property. To investigate the availability of iPSCs as bioengineered substitutes in corneal repair, we developed a thermo-gelling injectable amphiphatic carboxymethyl-hexanoyl chitosan (CHC) nanoscale hydrogel and found that such gel increased the viability and CD44 + proportion of iPSCs, and maintained their stem-cell like gene expression, in the presence of culture media. Combined treatment of iPSC with CHC hydrogel (iPSC/CHC hydrogel) facilitated wound healing in surgical abrasion-injured corneas. In severe corneal damage induced by alkaline, iPSC/CHC hydrogel enhanced corneal reconstruction by downregulating oxidative stress and recruiting endogenous epithelial cells to restore corneal epithelial thickness. Therefore, we demonstrated that these human keratocyte-reprogrammed iPSCs, when combined with CHC hydrogel, can be used as a rapid delivery system to efficiently enhance corneal wound healing. In addition, iPSCs reprogrammed from corneal surgical residues may serve as an alternative cell source for personalized therapies for human corneal damage. (C) 2012 Elsevier Ltd. All rights reserved.