Combinational application of corneal keratocyte-reprogrammed induced pluripotent stem cells and amphiphatic carboxymethyl-hexanoyl chitosan hydrogel for corneal repair

• Main Authors: Yi-Wen Liao, 廖翊妏
• Other Authors: Hen-Li Chen
• Format: Others
• Language: en_US
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/82880602423510488045

博士 === 國立陽明大學 === 口腔生物研究所 === 101 === Induced pluripotent stem cells (iPSCs) possess promising potential in regenerative medicine, but the ability of iPSCs to 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 with a serum- and feeder-free system in which they remained stable through 30 passages and showed ESC-like pluripotent property. To investigate the feasibility of iPSCs as bioengineered substitutes in corneal repair, a thermo-gelling injectable amphiphatic carboxymethyl-hexanoyl chitosan (CHC) nanoscale hydrogel was used as a carrier for iPSCs. The results indicated that CHC hydrogel increased the viability and CD44+ proportion of iPSCs, and maintained their stem-cell like gene expression. 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 cellular oxidative stress and recruiting endogenous epithelial cells to restore corneal epithelial thickness. Therefore, we demonstrated that human corneal keratocyte-reprogrammed iPSCs, delivered by CHC hydrogel, significantly enhance corneal wound healing. In addition, iPSCs derived from corneal surgical residues may serve as an alternative cell source for personalized therapies for human corneal damage.