ABSTRACT
In this study, we aimed to investigate the feasibility of directed differentiation of human amniotic epithelial cells into conjunctival epithelium under specific conditions as well as of constructing tissue-engineered conjunctiva for ocular surface reconstruction. Human amniotic epithelial cells were cultured with induced denuded conjunctival matrix and conjunctival homogenate. Immunohistochemistry of cytokeratin-4, cytokeratin-13, and muc5ac as well as PAS staining were performed. The concentration of muc5ac at different times was measured using ELISA. The differentiated cells with quantum dots were transferred onto a denuded amniotic membrane to establish tissue-engineered conjunctiva and transplanted into a rabbit model with a conjunctival defect. After induction of human amniotic epithelial cells, differentiated cells showed conjunctival epithelium phenotype, while trace amounts of mu5ac in the culture medium measured by ELISA increased gradually within 1 to 7 days. Successfully tissue-engineered conjunctiva had similar structure as normal conjunctiva and was transplanted into a rabbit model with conjunctiva defect. After 2 weeks post-surgery, conjunctiva grafts survived and were integrated. Immunohistochemistry showed conjunctival epithelium phenotype, positive cells were found in PAS staining. Thus, human amniotic epithelial cells could differentiate into conjunctival epithelium-like cells and goblet cells with partially physiological function, and we successfully restored ocular surface integrity in the rabbit model using tissue-engineered conjunctiva.
Subject(s)
Amnion/cytology , Cell Differentiation , Conjunctiva , Epithelial Cells/cytology , Regeneration , Amnion/metabolism , Animals , Biomarkers , Cell Transdifferentiation , Cells, Cultured , Epithelial Cells/metabolism , Female , Humans , Immunohistochemistry , Male , Models, Animal , Rabbits , Tissue EngineeringABSTRACT
We describe 8 patients affected with Costello syndrome including an affected sib pair and review the literature on 29 previously reported cases. We emphasize an association with advanced parental age, which is consistent with autosomal dominant inheritance with germline mosaicism. The pathogenesis appears to involve metabolic dysfunction, with growth disturbance, storage disorder appearance, acanthosis nigricans, hypertrophic cardiomyopathy, and occasional abnormalities of glucose metabolism. Although the cause is currently unknown, Costello syndrome is interesting because of a potential genetic-metabolic etiology.