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Wound healing revised: A novel reepithelialization mechanism revealed by in vitro and in silico models

Wound healing is a complex process in which a tissue’s individual cells have to be orchestrated in an efficient and robust way. We integrated multiplex protein analysis, immunohistochemical analysis, and whole-slide imaging into a novel medium-throughput platform for quantitatively capturing prolife...

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Detalles Bibliográficos
Autores principales: Safferling, Kai, Sütterlin, Thomas, Westphal, Kathi, Ernst, Claudia, Breuhahn, Kai, James, Merlin, Jäger, Dirk, Halama, Niels, Grabe, Niels
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3840932/
https://www.ncbi.nlm.nih.gov/pubmed/24385489
http://dx.doi.org/10.1083/jcb.201212020
Descripción
Sumario:Wound healing is a complex process in which a tissue’s individual cells have to be orchestrated in an efficient and robust way. We integrated multiplex protein analysis, immunohistochemical analysis, and whole-slide imaging into a novel medium-throughput platform for quantitatively capturing proliferation, differentiation, and migration in large numbers of organotypic skin cultures comprising epidermis and dermis. Using fluorescent time-lag staining, we were able to infer source and final destination of keratinocytes in the healing epidermis. This resulted in a novel extending shield reepithelialization mechanism, which we confirmed by computational multicellular modeling and perturbation of tongue extension. This work provides a consistent experimental and theoretical model for epidermal wound closure in 3D, negating the previously proposed concepts of epidermal tongue extension and highlighting the so far underestimated role of the surrounding tissue. Based on our findings, epidermal wound closure is a process in which cell behavior is orchestrated by a higher level of tissue control that 2D monolayer assays are not able to capture.