title: Corneal repair by human corneal keratocyte-reprogrammed iPSCs and amphiphatic carboxymethyl-hexanoyl chitosan hydrogel.
abstract: 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.
authors.affiliation: Institute of Oral Biology, National Yang-Ming University, Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: Yueh
authors.initials: Y
authors.lastname: Chien
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Liao
authors.forename: Dean-Mo
authors.initials: DM
authors.lastname: Liu
authors.forename: Heng-Liang
authors.initials: HL
authors.lastname: Lin
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Chen
authors.forename: Hen-Li
authors.initials: HL
authors.lastname: Chen
authors.forename: Chi-Hsien
authors.initials: CH
authors.lastname: Peng
authors.forename: Chang-Min
authors.initials: CM
authors.lastname: Liang
authors.forename: Chung-Yuan
authors.initials: CY
authors.lastname: Mou
authors.forename: Shih-Hwa
authors.initials: SH
authors.lastname: Chiou
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D048271:Chitosan / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003315:Cornea / Q000166:cytology / Q000187:drug effects* / Q000473:pathology*; D060527:Corneal Keratocytes / Q000166:cytology*; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000627:therapeutic use*; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000637:transplantation*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D014945:Wound Healing / Q000187:drug effects*
chemical_list: C522410:carboxymethyl-hexanoyl chitosan; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D048271:Chitosan