Histological, histochemical, and immunohistochemical characterization of NANOULCOR nanostructured fibrin‑agarose human cornea substitutes generated by tissue engineering
Metadatos
Mostrar el registro completo del ítemAutor
Ortiz Arrabal, Olimpia; Blanco Elices, Cristina; González Gallardo, Carmen; Sanchez Porras, David; Etayo Escanilla, Miguel; Ávila-Fernández, Paula; Chato Astrain, Jesús; García García, Oscar Darío; Garzón Bello, Ingrid Johanna; Alaminos Mingorance, MiguelEditorial
Springer Nature
Materia
Cornea Tissue engineering Limbal stem cells
Fecha
2024-11-13Referencia bibliográfica
Ortiz Arrabal, O. et. al. BMC Med 22, 531 (2024). [https://doi.org/10.1186/s12916-024-03759-4]
Patrocinador
Instituto de Salud Carlos III (ISCIII), Ministry of Science, Innovation and Universities, grants FIS PI23/00335, FIS PI20/00317, and ICI21/00010 (NANOULCOR); Grant CSyF PI-0086–2020 from Consejería de Salud y Consumo, Junta de Andalucía, Spain; Grant B-CTS-504-UGR20 (Programa Operativo FEDER Andalucía 2014-2020, University of Granada and Consejería de Universidad, Investigación e Innovacin).; European Regional Development Fund (ERDF) through the “Una manera de hacer Europa” programResumen
Background Human artificial corneas (HAC) generated by tissue engineering recently demonstrated clinical usefulness
in the management of complex corneal diseases. However, the biological mechanisms associated to their regenerative
potential need to be elucidated.
Methods In the present work, we generated HAC using nanostructured fibrin-agarose biomaterials with cultured
corneal epithelial and stromal cells, and we compared the structure and histochemical and immunohistochemical
profiles of HAC with control native corneas (CTR-C) and limbus (CTR-L) to determine the level of biomimicry
of the HAC with these two native organs.
Results HAC tissues consisted of a stratified epithelium and a cellular stromal substitute. The interface
between stroma and epithelium was similar to that of CTR-C, without the finger-shaped palisades of Vogt found
in CTR-L, and contained a poorly developed basement membrane as determined by PAS histochemistry. Analysis
of the stromal layer revealed that HAC contained significantly lower amounts of extracellular matrix components
(collagen, proteoglycans, decorin, keratocan, and lumican) than CTR-C and CTR-L, with all samples being devoid
of elastic and reticular fibers. At the epithelial level, HAC were strongly positive for several cytokeratins, although KRT5
was lower in HAC as compared to CTR-C and CTR-L. The expression of crystallin lambda was lower in HAC than in control
tissues, whereas crystallin alpha-a was similar in HAC and CTR-C. No differences were found among HAC and controls
for the cell–cell junction proteins CX43 and TJP1. When specific markers were analyzed, we found that HAC
expression profile of KRT3, KRT19, KRT15, and ΔNp63 was more similar to CTR-L than to CTR-C. Conclusions These results suggest that HAC generated in the laboratory could be structurally and functionally more
biomimetic to the structure found at the corneal limbus than to the central cornea, and open the door to the use
of these artificial tissues in patients with limbal deficiency.