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Microenvironmental regulation of corneal limbal epithelial cells cultured on denuded amniotic membrane: emphasis in supramolecular organization of major extracellular biopolymers

Grant number: 13/25533-1
Support type:Scholarships in Brazil - Master
Effective date (Start): March 01, 2014
Effective date (End): July 31, 2015
Field of knowledge:Agronomical Sciences - Veterinary Medicine
Principal Investigator:José Luiz Laus
Grantee:Gisele Pereira Valdetaro
Home Institution: Faculdade de Ciências Agrárias e Veterinárias (FCAV). Universidade Estadual Paulista (UNESP). Campus de Jaboticabal. Jaboticabal , SP, Brazil


Evolution of risk/benefit that accompanies the bioengineered tissues used for reconstruction of ocular surfaces with limbal stem cell deficiency depends on new ideas and methodological approaches for studying the microenvironmental regulation of corneal limbal epithelial progenitor cells and developing a new generation of substrates/membranes susceptible for expansion of them. Clearly, emphasis have been given to the role of biochemical cues (involving soluble molecules) in regulating corneal limbal epithelium cultured on different substrates, especially denuded amniotic membrane (routinely used in ophthalmology reference centers). In contrast, epithelium regulation by biophysical cues related to supramolecular organization of extracellular biopolymers into the limbus (in the case of explant culture system) and the cell expansion/attachment substrate has been poorly studied. It is known that supraorganization (molecular order) create cell-matrix interaction sites that are able for activating/deactivating mechanotransduction pathways and for enhancing/neutralizing the action of growth and survival factors. At least five structural properties of denuded amniotic membrane, which can contribute to phenotypic modulation and polarization of cultured cells, are associated with extracellular matrix supraorganization: geometry, topography, spatial orientation, stiffness/elasticity, and force. With advances in nanotechnology, material science and supramolecular chemistry, the perspective of exploring a supraorganization (reflecting nanoscale applications) for subsequently create synthetic biomimetics membranes become true. Several recent studies concluded that the future of regenerative medicine is nano and supra. Thus, the main goal of this research is to evaluate the supramolecular organization of the major biopolymers (ie. collagens and proteoglycans) of the extracellular matrix from denuded amniotic membrane combined with limbal explants in therapeutic cell culture systems for corneal surface reconstruction. The optical phenomena resulting from the interaction of extracellular matrix supraorganization with electromagnetic radiation will form the basis of our analyses.

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
VALDETARO, GISELE P.; ALDROVANI, MARCELA; PADUA, IVAN R. M.; CRISTOVAM, PRISCILA C.; GOMES, JOSE A. P.; LAUS, JOSE L. Supra-organization and optical anisotropies of the extracellular matrix in the amniotic membrane and limbal stroma before and after explant culture. BIOMEDICAL OPTICS EXPRESS, v. 7, n. 12, p. 4982-4994, DEC 1 2016. Web of Science Citations: 2.
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
VALDETARO, Gisele Pereira. Regulação microambiental de células epiteliais límbicas corneais de coelho expandidas sobre membrana amniótica humana desepitelizada : ênfase para a organização supramolecular dos maiores biopolímeros extracelulares. 2015. Master's Dissertation - Universidade Estadual Paulista "Júlio de Mesquita Filho" Faculdade de Ciências Agrárias e Veterinárias..

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