RESUMEN
The microvasculature within the neural stem cell (NSC) niche promotes self-renewal and regulates lineage progression. Previous work identified endothelial-produced soluble factors as key regulators of neural progenitor cell (NPC) fate and proliferation; however, endothelial cells (ECs) are sensitive to local hemodynamics, and the effect of this key physiological process has not been defined. In this study, we evaluated adult mouse NPC response to soluble factors isolated from static or dynamic (flow) EC cultures. Endothelial factors generated under dynamic conditions significantly increased neuronal differentiation, while those released under static conditions stimulated oligodendrocyte differentiation. Flow increases EC release of neurogenic factors and of heparin sulfate glycosaminoglycans that increase their bioactivity, likely underlying the enhanced neuronal differentiation. Additionally, endothelial factors, especially from static conditions, promoted adherent growth. Together, our data suggest that blood flow may impact proliferation, adhesion, and the neuron-glial fate choice of adult NPCs, with implications for diseases and aging that reduce flow.
Asunto(s)
Células Madre Adultas/citología , Adhesión Celular , Linaje de la Célula , Proliferación Celular , Células Endoteliales/citología , Células-Madre Neurales/citología , Células Madre Adultas/metabolismo , Células Madre Adultas/fisiología , Animales , Encéfalo/irrigación sanguínea , Encéfalo/citología , Diferenciación Celular , Células Cultivadas , Células Endoteliales/metabolismo , Células Endoteliales/fisiología , Endotelio Vascular/citología , Femenino , Glicosaminoglicanos/metabolismo , Ratones , Células-Madre Neurales/metabolismo , Células-Madre Neurales/fisiología , Neuropéptidos/metabolismo , Nicho de Células MadreRESUMEN
BACKGROUND: Despite their frequency in clinical practice, controversy exists regarding the significance and management of dysplastic nevi (DN). Although the perception of DN as precursors to melanoma is questionable, excisions of biopsy-proven DN are commonplace in clinical practice. The management of dysplastic acral nevi is of interest given the challenge of surgery at acral sites. OBJECTIVE: To determine the outcomes of biopsies of clinically atypical acral nevi and excisions of histologically dysplastic acral nevi (HDN). MATERIALS AND METHODS: Retrospective review of consecutive patients at a private dermatology practice who had a biopsy of an atypical acral nevus from December 2004 to July 2012. RESULTS: One hundred eighty-seven atypical acral nevi were biopsied from 168 patients (77 (41%) HDN, 108 (58%) common nevi). Based on initial histology, 30 (39%) HDN were recommended for excision and eight (10%) for clinical observation. Twenty-seven of the 77 HDN were excised; 23 (85%) revealed scar only, and four (15%) revealed residual DN not involving the margin. CONCLUSION: Routine excision of biopsy-proven dysplastic acral nevi may not be necessary.