Smart biomaterials play a key role when aiming at successful tissue repair by means of regenerative medicine approaches, and are expected to contain chemical as well as mechanical cues that will guide the regenerative process. Recent advances in the understanding of stem cell biology and mechanosensing have shed new light onto the importance of the local microenvironment in determining cell fate. Herein we report the biological properties of a bioactive, biodegradable calcium phosphate glass/polylactic acid composite biomaterial that promotes bone marrow-derived endothelial progenitor cell (EPC) mobilisation, differentiation and angiogenesis through the creation of a controlled bone healing-like microenvironment. The angiogenic response is triggered by biochemical and mechanical cues provided by the composite, which activate two synergistic cell signalling pathways: a biochemical one mediated by the calcium-sensing receptor and a mechanosensitive one regulated by non-muscle myosin II contraction. Together, these signals promote a synergistic response by activating EPCs-mediated VEGF and VEGFR-2 synthesis, which in turn promote progenitor cell homing, differentiation and tubulogenesis. These findings highlight the importance of controlling microenvironmental cues for stem/progenitor cell tissue engineering and offer exciting new therapeutical opportunities for biomaterialbased vascularisation approaches and clinical applications.
Angiogenesis is a complex process regulated by many cell types and a large variety of biochemical signals such as growth factors, transcription factors, oxygen and nutrient diffusion among others. In the present study, we found out that Flk-1(+) CD34(+) progenitor cells (bone marrow resident cells with an important role in angiogenesis) were responsive to changes in extracellular calcium concentration through a membrane bound, G-protein-coupled receptor sensitive to calcium ions related to the calcium-sensing receptor (CaSR). Calcium was able to induce progenitor cell migration in Boyden chamber experiments and tubulogenesis in Matrigel assays. Addition of anti-CaSR antibodies completely blocked the effect, while CaSR agonist Mg2+ produced a similar response to that of calcium. Real time RT-PCR for a wide array of angiogenesis-related genes showed increased expression of endothelial markers and signaling pathways involved in angiogenesis. These results suggest calcium could be a physiological modulator of the bone marrow progenitor cell-mediated angiogenic response.
Las cookies son importantes para ti, influyen en tu experiencia de navegación, nos ayudan a proteger tu privacidad y permiten realizar las peticiones que nos solicites a través de la web. Utilizamos cookies propias y de terceros para analizar nuestros servicios y mostrarte publicidad relacionada con tus preferencias en base a un perfil elaborado con tus hábitos de navegación. Puedes "Aceptar" o "Rechazar" aquellas cookies que no sean técnicas, así como configurar tus preferencias pulsando "Configurar Cookies". Más información, consulta nuestra Política de Cookies.
Funcionales
Siempre activo
El almacenamiento o acceso técnico es estrictamente necesario para el propósito legítimo de permitir el uso de un servicio específico solicitado explícitamente por el abonado o el usuario, o con el único fin de llevar a cabo la transmisión de una comunicación a través de una red de comunicaciones electrónicas.
Preferences
The technical storage or access is necessary for the legitimate purpose of storing preferences that are not requested by the subscriber or user.
Statistics
The technical storage or access that is used exclusively for statistical purposes.El almacenamiento o acceso técnico que se utiliza exclusivamente con fines estadísticos anónimos. Sin una orden judicial, el cumplimiento voluntario por parte de su proveedor de servicios de Internet, o registros adicionales de un tercero, la información almacenada o recuperada con este único propósito no puede utilizarse normalmente para identificarle.
Marketing
El almacenamiento o acceso técnico es necesario para crear perfiles de usuario con el fin de enviar publicidad, o para rastrear al usuario en un sitio web o en varios sitios web con fines de marketing similares.
Aguirre, A., Gonzalez, A., Navarro, M., Castano, O., Planell, J. A., Engel, E., (2012). Control of microenvironmental cues with a smart biomaterial composite promotes endothelial progenitor cell angiogenesis 
European Cells & Materials , 24, 90-106