RESUMEN
Loss of sensory innervation delays wound healing and administration of the neuropeptide substance P improves re-epithelialization. Keratinocyte hyperproliferation post-wounding may result from symmetric stem cell (SC) self-renewal, asymmetric SC self-renewal, committed progenitor divisions, or a combination of these. However, the effects of sensory denervation and of neuropeptides on SC proliferation are not known. Here we show that early after wounding both asymmetric and symmetric SC self-renewal increase, without significant committed progenitor (CP) activation. Decreased sensory innervation is associated with a decrease in both SC and CP proliferation. Based on previous work showing that substance P is decreased in capsaicin-treated mice and improves wound healing in normal skin, we examined the effects of substance P on SC and CP proliferation during wound healing. Substance P restored asymmetric SC proliferation in skin with decreased sensory innervation, both at baseline and following wounding. Epidermis with decreased sensory innervation was severely thinned. Consistent with this, substance P-induced asymmetric SC proliferation resulted in increased stratification in skin with both normal and decreased innervation. Lapatinib prevented the substance P-induced increase in asymmetric SC divisions in murine epidermis, as well as the increase in epidermal stratification, suggesting that asymmetric SC divisions are required for epidermal stratification.
RESUMEN
The study of stem cells in the epidermis is a rapidly emerging field. Great advances have been made in both basic and clinical research. Advances in basic science include the ability to assay stem cells of the epidermis in vivo, new strong evidence for the existence of an independent interfollicular epidermal stem cell, and improved ability to analyze individual stem cell divisions. Advances in the clinic include recognition of the importance of stem cells for wound repair and for gene therapy and promising results have been obtained in a patient with junctional epidermolysis bullosa over a 12 month period of observation. This article discusses these recent advances in cutaneous stem cell biology.
Asunto(s)
Dermatología/tendencias , Células Epidérmicas , Células Madre/citología , Adulto , Envejecimiento/patología , Animales , Diferenciación Celular , División Celular , Linaje de la Célula , Polaridad Celular , Células Cultivadas/citología , Preescolar , Epidermis/crecimiento & desarrollo , Epidermólisis Ampollosa/cirugía , Terapia Genética , Folículo Piloso/citología , Proteínas Hedgehog/fisiología , Humanos , Lactante , Recién Nacido , Queratinocitos/citología , Masculino , Ratones , Ratones Mutantes , Persona de Mediana Edad , Modelos Biológicos , Ratas , Trasplante de Células Madre , Células Madre/clasificación , Cicatrización de Heridas/fisiologíaRESUMEN
Advances in tissue engineering of skin are needed for clinical applications (as in wound healing and gene therapy) for cutaneous and systemic diseases. In this paper we review the use of epidermal stem cells as a source of cells to improve tissue-engineered skin. We discuss the importance and limitations of epidermal stem cell isolation using biomarkers, in quest of a pure stem cell preparation, as well as the culture conditions necessary to maintain this purity as required for a qualitatively superior and long-lasting engineered skin. Finally, we review the advantages of using additional multipotent stem cell sources to functionally and cosmetically optimize the engineered tissue.