RESUMO
Extensive skin damage requires specialized therapy that stimulates regeneration processes without scarring. The possibility of using combination of a collagen gel application as a wound dressing and fibroblast attractant with verteporfin as an antifibrotic agent was examined in vivo and in vitro. In vitro effects of verteporfin on viability and myofibroblast markers expression were evaluated using fibroblasts isolated from human scar tissue. In vivo the collagen gel and verteporfin (individually and in combination) were applied into the wound to investigate scarring during skin regeneration: deviations in skin layer thickness, collagen synthesis, and extracellular matrix fibers were characterized. The results indicate that verteporfin reduces fibrotic phenotype by suppressing expression of the contractile protein Sm22α without inducing cell death. However, administration of verteporfin in combination with the collagen gel disrupts its ability to direct wound healing in a scarless manner, which may be related to incompatibility of the mechanisms by which collagen and verteporfin control regeneration.
Assuntos
Colágeno , Fibroblastos , Verteporfina , Verteporfina/farmacologia , Verteporfina/uso terapêutico , Humanos , Colágeno/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Animais , Cicatrização/efeitos dos fármacos , Antifibróticos/farmacologia , Antifibróticos/uso terapêutico , Células Cultivadas , Alicerces Teciduais/química , Cicatriz/tratamento farmacológico , Cicatriz/patologia , Cicatriz/metabolismo , Masculino , Fibrose , Pele/efeitos dos fármacos , Pele/patologia , Pele/metabolismoRESUMO
Most of the knowledge about human skin homeostasis, development, wound healing, and diseases has been accumulated from human skin biopsy analysis by transferring from animal models and using different culture systems. Human-to-mouse xenografting is one of the fundamental approaches that allows the skin to be studied in vivo and evaluate the ongoing physiological processes in real time. Humanized animals permit the actual techniques for tracing cell fate, clonal analysis, genetic modifications, and drug discovery that could never be employed in humans. This review recapitulates the novel facts about mouse skin self-renewing, regeneration, and pathology, raises issues regarding the gaps in our understanding of the same options in human skin, and postulates the challenges for human skin xenografting.