title: Stable corneal regeneration four years after implantation of a cell-free recombinant human collagen scaffold.
abstract: We developed cell-free implants, comprising carbodiimide crosslinked recombinant human collagen (RHC), to enable corneal regeneration by endogenous cell recruitment, to address the worldwide shortage of donor corneas. Patients were grafted with RHC implants. Over four years, the regenerated neo-corneas were stably integrated without rejection, without the long immunosuppression regime needed by donor cornea patients. There was no recruitment of inflammatory dendritic cells into the implant area, whereas, even with immunosuppression, donor cornea recipients showed dendritic cell migration into the central cornea and a rejection episode was observed. Regeneration as evidenced by continued nerve and stromal cell repopulation occurred over the four years to approximate the micro-architecture of healthy corneas. Histopathology of a regenerated, clear cornea from a regrafted patient showed normal corneal architecture. Donor human cornea grafted eyes had abnormally tortuous nerves and stromal cell death was found. Implanted patients had a 4-year average corrected visual acuity of 20/54 and gained more than 5 Snellen lines of vision on an eye chart. The visual acuity can be improved with more robust materials for better shape retention. Nevertheless, these RHC implants can achieve stable regeneration and therefore, represent a potentially safe alternative to donor organ transplantation.
authors.affiliation: Integrative Regenerative Medicine Centre, Dept. of Clinical and Experimental Medicine, Cell Biology Bldg. - Level 10, Linköping University, SE-581 85 Linköping, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Fagerholm
authors.affiliation: Integrative Regenerative Medicine Centre, Dept. of Clinical and Experimental Medicine, Cell Biology Bldg. - Level 10, Linköping University, SE-581 85 Linköping, Sweden.
authors.forename: Neil S
authors.initials: NS
authors.lastname: Lagali
authors.affiliation: Department of Ophthalmology, Maisonneuve-Rosemont Hospital, 5415 Boulevard de L'Assomption, Montreal, QC, H1T 2M4, Canada.
authors.forename: Jeb A
authors.initials: JA
authors.lastname: Ong
authors.affiliation: Integrative Regenerative Medicine Centre, Dept. of Clinical and Experimental Medicine, Cell Biology Bldg. - Level 10, Linköping University, SE-581 85 Linköping, Sweden; Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada.
authors.forename: Kimberley
authors.initials: K
authors.lastname: Merrett
authors.affiliation: Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada.
authors.forename: W Bruce
authors.initials: WB
authors.lastname: Jackson
authors.affiliation: FibroGen, Inc. 409 Illinois Street, San Francisco, CA 94158, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: Polarek
authors.affiliation: Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario K1Y 4W7, Canada.
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Suuronen
authors.affiliation: CooperVision Inc., 5870 Stoneridge Drive, Suite 1, Pleasanton, CA 94588, USA.
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Ophthalmology, Maisonneuve-Rosemont Hospital, 5415 Boulevard de L'Assomption, Montreal, QC, H1T 2M4, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Brunette
authors.affiliation: Integrative Regenerative Medicine Centre, Dept. of Clinical and Experimental Medicine, Cell Biology Bldg. - Level 10, Linköping University, SE-581 85 Linköping, Sweden; FibroGen, Inc. 409 Illinois Street, San Francisco, CA 94158, USA. Electronic address: May.Griffith@liu.se.
authors.forename: May
authors.initials: M
authors.lastname: Griffith
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001672:Biocompatible Materials / Q000627:therapeutic use*; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D003315:Cornea / Q000601:surgery*; D005260:Female; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D019736:Prostheses and Implants; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*; D012038:Regeneration / Q000502:physiology*; D054457:Tissue Scaffolds / Q000737:chemistry*; D014792:Visual Acuity; D055815:Young Adult
chemical_list: D001672:Biocompatible Materials; D011994:Recombinant Proteins; D003094:Collagen
keywords: Collagen; Cornea; Recombinant protein; Transplantation