Abstract
PurposeHuman cornea substitutes generated by tissue engineering currently require limbal stem cells for the generation of orthotypical epithelial cell cultures. We recently reported that bioengineered corneas can be fabricated in vitro from a heterotypical source obtained from Wharton’s jelly in the human umbilical cord (HWJSC).MethodsHere, we generated a partial thickness cornea model based on plastic compression nanostructured fibrin-agarose biomaterials with cornea epithelial cells on top, as an orthotypical model (HOC), or with HWJSC, as a heterotypical model (HHC), and determined their potential in vivo usefulness by implantation in an animal model.ResultsNo major side effects were seen 3 and 12 months after implantation of either bioengineered partial cornea model in rabbit corneas. Clinical results determined by slit lamp and optical coherence tomography were positive after 12 months. Histological and immunohistochemical findings demonstrated that in vitro HOC and HHC had moderate levels of stromal and epithelial cell marker expression, whereas in vivo grafted corneas were more similar to control corneas.ConclusionThese results suggest that both models are potentially useful to treat diseases requiring anterior cornea replacement, and that HHC may be an efficient alternative to the use of HOC which circumvents the need to generate cornea epithelial cell cultures.
Highlights
Transplantation of a functional tissue-engineered cornea could contribute to the clinical treatment of patients with severe corneal defects (Garzon et al, 2014b; Gonzalez-Andrades et al, 2017)
On the other hand, promising models of bioartificial corneas have been developed by tissue engineering (Ghezzi et al, 2015), including full-thickness corneas (Griffith et al, 1999; Alaminos et al, 2006) and anterior lamellar partial thickness corneas consisting of an epithelial layer with cornea epithelial cells and a subjacent stromal layer with biomaterials and keratocytes (Gonzalez-Andrades et al, 2009; Mi et al, 2010; Zaniolo et al, 2013; Couture et al, 2016; Rico-Sanchez et al, 2019)
Macroscopic examination of the rabbit eyes revealed that human orthotypical cornea (HOC) and human heterotypical cornea (HHC) resulted in corneas with some inflammatory signs around the suture stitches, especially 3 months after in vivo implantation
Summary
Transplantation of a functional tissue-engineered cornea could contribute to the clinical treatment of patients with severe corneal defects (Garzon et al, 2014b; Gonzalez-Andrades et al, 2017). The clinical translation potential of most of these strategies is still uncertain and highly dependent on the availability of adequate limbal stem cell sources for the generation of bioengineered cornea models with corneal cells. In this regard, human limbal stem cell cultures raised from limbal biopsies are difficult to obtain, and the procedure is subjected to the risk of causing limbal stem-cell deficiency in the healthy eye (Nishida et al, 2004)
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