1+1=3 the emergent properties of patterned materials / Capacidad remielinizante de vesículas extracelulares enriquecidas en el miR219a-5p y su potencial aplicación terapéutica en la Esclerosis Múltiple: paso a paso.

1+1=3 the emergent properties of patterned materials

Tissue engineering involves assembling functional cells tailored to perform specific functions. Biological tissues are anisotropic and present spatial gradients in architecture and composition. This study explores a novel approach to guide human mesenchymal stromal cells (hMSCs) behavior by encapsulation in photo-patterned alginate hydrogels. Two different crosslinked sections, degradable (Deg) vs. non-degradable (noDeg), are created dependent on the light exposure (UV and crosslinking with matrix metalloprotease (MMP) sensitive peptide vs. nonUV and click crosslinking). The patterned alginate hydrogels harbor a Deg phase, with cell spreading, collective cell alignment and preferential osteogenic differentiation; and a noDeg phase, with rounded cells, no preferential alignment and higher adipogenic differentiation. The previous patterns in cell behavior are observed under growth media (in absence of biochemical stimuli) and potentiated in the presence of specific conditioned media. We confirm the involvement of mechanotransduction pathways by the integrin-mediated yes-associated protein (YAP) nuclear translocation within degradable zones, while a homogeneous cytoplasmic/nuclear distribution is evident in non-degradable zones. The patterns in cell morphology are dependent on matrix degradation and integrin-binding, as no patterns are seen using an MMP-scramble peptide or no-RGD materials. Thus, 3D patterns in hydrogel degradation spatially guide YAP nuclear translocation and hMSC osteogenic differentiation. The spatial patterns in degradation are a step closer to mimic the 3D anisotropy of tissues, by allowing to segregate cell behavior. This opens new opportunities for fundamental understanding of guided collective cell behavior and tissue engineering applications.

Capacidad remielinizante de vesículas extracelulares enriquecidas en el miR219a-5p y su potencial aplicación terapéutica en la Esclerosis Múltiple: paso a paso.

la esclerosis múltiple es una enfermedad inmunomediada, desmilinizante y neurodegenerativa crónica que afecta a más de 2,5 millones de personas en todo el mundo. A pesar de que se pueden encontrar varios medicamentos moduladores de la enfermedad en el mercado, hoy en día no existen fármacos que aborden la parte neurodegenerativa de la enfermedad. Es por ello que se propone una nueva aproximación farmacológica mediante el uso de vesículas extracelulares enriquecidas en el miR219a-5p como posible tratamiento neuroprotector y/o neuroreparador. No obstante, es de crucial importancia realizar una caracterización exhaustiva previa del producto que se pretende llevar a la clínica para poder avanzar sobre pasos seguros y robustos.