Terapia celular asistida por hidrogeles de fibroína en un modelo experimental de ictus cerebral

Abstract

ABSTRACT Stroke is a leading cause of adult disability (including paralysis) and cognitive impairment and the second-leading global cause of death behind ischemic heart disease. It is estimated that 25-53% of patients remain dependent for at least one daily task up to 6 months after stroke, globally producing incalculable personal, family and social costs. Currently there are not therapies available to repair the damaged brain tissue and promote a satisfactory degree of functional recovery in patients. In recent decades, a considerable progress has been made in the development of experimental therapies to treat brain disorders. Among the different experimental approaches examined in the last decades, cell therapy has been configured as a viable option for restoring damaged brain areas with new cerebral tissue derived from exogenous implanted cells as well as for stimulating endogenous brain repair mechanisms. The relevance of this approach has been seen in later years, with a progressive expansion of clinical trials that have included patients with cerebral damage transplanted with different cell populations through systemic or intracerebral routes. The combined implantation of cells and different biomaterials to increase the viability of cellular grafts constitutes a very promising strategy in phase of full expansion. Due to its special chemical and physical structure with stiffness modules in the range of soft tissues like the brain, hydrogels appear a versatile and interesting group of architectonic elements for cell encapsulation and brain reconstruction. In this study, we show a novel therapeutic approach based on the combined implantation of mesenchymal stem cells and silk fibroin-based hydrogels as a support for brain stroke treatment. Firstly, we have demonstrated the innocuousness and tolerability of this biomaterial with brain tissue and function as well as its ability to favor cellular engraftment after brain implantation. Secondly, in an experimental stroke model in mice we have shown that this strategy favors neuroprotection and functional remodeling between cortical representations, being this latter, substrate for post-stroke neuro-restoration and functional recovery.