title: Biocompatibility and functionality of a tissue-engineered living corneal stroma transplanted in the feline eye.
abstract: OBJECTIVE
  Corneal tissue shortage has become a major concern worldwide, which has motivated the search for alternative solutions to eye bank human eyes for corneal transplantation. Minimally invasive lamellar transplantation and tissue engineering may offer new opportunities for the rehabilitation of diseased corneas. The aim of this study was to evaluate the biocompatibility and functionality of stromal lamellar grafts tissue-engineered (TE) in vitro and transplanted in vivo in the cornea of a feline model.
  
  
  METHODS
  The corneal stromas were engineered in culture from corneal stromal cells using the self-assembly approach, without the addition of exogenous material or scaffold. Eight healthy animals underwent two intrastromal grafts in one eye and the contralateral eye was used as a control. Animals were followed with slit-lamp ophthalmic examination, corneal esthesiometry and optical coherent tomography. Confocal microscopy, immunofluorescence, histology, and transmission electron microscopy (TEM) were performed at 4 months.
  
  
  RESULTS
  Four months after transplantation, the TE-stromal grafts were transparent, functional, and well tolerated by the eye. All grafts remained avascular, with no signs of immune rejection, despite a short course of low-dose topical steroids. Corneal sensitivity returned to preoperative level and reinnervation of the grafts was confirmed by confocal microscopy and immunofluorescence. Histology and TEM of the TE-grafts showed a lamellar stromal structure with regular collagen fibril arrangement.
  
  
  CONCLUSIONS
  These results open the way to an entirely new therapeutic modality. Intracorneal filling using a biocompatible, transparent, and malleable TE-stroma could be the basis for multiple types of novel therapeutic options in corneal interventional surgery.
authors.affiliation: Maisonneuve-Rosemont Hospital Research Center, Montreal, Québec, Canada Département d'ophtalmologie, Université d'Aix-Marseille, Marseille, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Boulze Pankert
authors.affiliation: Centre de recherche du CHU de Québec, Axe médecine régénératrice, Hôpital St-Sacrement, CUO-Recherche, and Centre de recherche en organogenèse expérimentale de l'Université Laval/LOEX, Québec City, Québec, Canada.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Goyer
authors.affiliation: Maisonneuve-Rosemont Hospital Research Center, Montreal, Québec, Canada.
authors.forename: Fatma
authors.initials: F
authors.lastname: Zaguia
authors.affiliation: Maisonneuve-Rosemont Hospital Research Center, Montreal, Québec, Canada.
authors.forename: Myriam
authors.initials: M
authors.lastname: Bareille
authors.affiliation: Maisonneuve-Rosemont Hospital Research Center, Montreal, Québec, Canada.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Perron
authors.affiliation: Maisonneuve-Rosemont Hospital Research Center, Montreal, Québec, Canada Department of Ophthalmology, University of Montreal, Montreal, Québec, Canada.
authors.forename: Xinling
authors.initials: X
authors.lastname: Liu
authors.affiliation: Ophthalmology and Visual Neurosciences and Laboratory Medicine and Pathology, University of Minnesota School of Medicine, Minneapolis, Minnesota, United States.
authors.forename: J Douglas
authors.initials: JD
authors.lastname: Cameron
authors.affiliation: Centre de recherche du CHU de Québec, Axe médecine régénératrice, Hôpital St-Sacrement, CUO-Recherche, and Centre de recherche en organogenèse expérimentale de l'Université Laval/LOEX, Québec City, Québec, Canada Département d'ophtalmologie et d'oto-rhino-laryngologie - chirurgie maxillo-faciale, Faculté de médecine, Université Laval, Québec City, Québec, Canada.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Proulx
authors.affiliation: Maisonneuve-Rosemont Hospital Research Center, Montreal, Québec, Canada Department of Ophthalmology, University of Montreal, Montreal, Québec, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Brunette
mesh_terms: D000328:Adult; D000818:Animals; D002415:Cats; D002478:Cells, Cultured; D003319:Corneal Stroma / Q000637:transplantation* / Q000648:ultrastructure; D016039:Corneal Transplantation / Q000379:methods*; D004195:Disease Models, Animal; D004728:Endothelium, Corneal / Q000648:ultrastructure; D006085:Graft Survival; D006650:Histocompatibility Testing / Q000379:methods; D006801:Humans; D018613:Microscopy, Confocal; D023822:Tissue Engineering; D041623:Tomography, Optical Coherence; D014183:Transplantation, Heterologous
keywords: cell culture; corneal stroma; corneal substitute; corneal transplantation; reinnervation; tissue engineering