July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Recombinant human collagen type I hydrogels as superior cell carriers for corneal epithelial stem cells and corneal transplantation.
Author Affiliations & Notes
  • Michel Haagdorens
    University of Antwerp, Edegem, Belgium
    Antwerp University Hospital, Belgium
  • Aneta Liszka
    Linköping University, Sweden
  • Monika ljunggren
    Linköping University, Sweden
  • per fagerholm
    Linköping University, Sweden
  • Ramunas valiokas
    Ferentis UAB, Lithuania
    center for physical sciences and technology, Lithuania
  • Vytautas Cepla
    center for physical sciences and technology, Lithuania
  • Yehiel Tal
    Collplant, Israel
  • nadav orr
    Collplant, Israel
  • Tsvika shtein
    Hebrew University, Israel
  • oded shoseyov
    Hebrew University, Israel
  • sofie thys
    University of Antwerp, Edegem, Belgium
  • isabel pintelon
    University of Antwerp, Edegem, Belgium
  • May Griffith
    Maisonneuve, Université de Montréal, Quebec, Canada
  • Marie-José Tassignon
    University of Antwerp, Edegem, Belgium
  • Footnotes
    Commercial Relationships   Michel Haagdorens, None; Aneta Liszka, None; Monika ljunggren, None; per fagerholm, None; Ramunas valiokas, Ferentis (E); Vytautas Cepla, None; Yehiel Tal, Collplant (P), Collplant (E); nadav orr, Collplant (E), Collplant (P); Tsvika shtein, None; oded shoseyov, None; sofie thys, None; isabel pintelon, None; May Griffith, None; Marie-José Tassignon, None
  • Footnotes
    Support  ENM grant G0D5615N
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 4139. doi:
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      Michel Haagdorens, Aneta Liszka, Monika ljunggren, per fagerholm, Ramunas valiokas, Vytautas Cepla, Yehiel Tal, nadav orr, Tsvika shtein, oded shoseyov, sofie thys, isabel pintelon, May Griffith, Marie-José Tassignon; Recombinant human collagen type I hydrogels as superior cell carriers for corneal epithelial stem cells and corneal transplantation.. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4139.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Cornea transplantation suffers from a severe global shortfall, with over 12 million patients worldwide awaiting transplantation according to the WHO. Therefore there is a high need for tissue-engineered alternative that can replace conventional corneal grafting. The aim of this study is to investigate recombinant human collagen type I (RHCI) hydrogels as a substitute corneal transplant.

Methods : In vitro biocompatibility of RHC I hydrogels was tested in a genotoxicity (VITOTOX), cell viability (PrestoBlue) and proliferation (BrdU) assay. Composite grafts were generated using primary limbal epithelial stem cells (LESC) and characterized using immunohistochemistry, electron micrscopy and qPCR analysis. To test bio-integration and degradation, acellular hydrogels were implanted as a corneal implant in mini-pigs with a follow-up of 1 year.

Results : RHCI generates transparent and ultrathin hydrogels that withstand manipulation. Hydrogels show no genotoxic effect, and cell tend to adhere and proliferate well to the hydrogel with cell viability and total outgrowth being comparable to tissue culture plastic and amnion. When cultivated on RHCI, primary LESC keep expressing their undifferentiated adherent stem cell genotype and phenotype. In vivo, RHCI hydrogels show good biocompatibility as hydrogels remain intact, transparent, elicit minimal inflammation and integrate within the surrounding tissue. No difference was observed with control allografted corneas in the animal model.

Conclusions : Primary LESCs can successfully be cultivated on RHCI hydrogels using a standardized xeno-free GMP-grade cultivation protocol. Its favorable optical characteristics, relative microbial resistance, successful composite graft generation and biocompatibility prove that RHCI is a highly promising scaffold for ocular tissue engineering. The hydrogels will be brought into humans as a first-in-human trial in 2020.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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