Bone marrow mesenchymal stem cells loaded into hydrogel/nanofiber composite scaffolds ameliorate ischemic brain injury

Abstract

Central nervous system (CNS) function recovery following stroke remains a major challenge because neural regeneration is difficult to achieve. In this study, rigid-flexible composite scaffolds consisting of nanofibers from electrospun scaffolds and self-adapting and injectable hydrogel were loaded with bone marrow mesenchymal stem cells (BMSCs), and the effects of these loaded BMSCs on ischemic insult were investigated. In vitro analysis of the viability, migration, neurite growth, angiogenic capacity, and paracrine effects of BMSCs indicated that BMSCs loaded in composite scaffolds had a better therapeutic effect than those BMSCs in saline. Furthermore, in vivo, BMSCs loaded in composite scaffolds significantly reduced the extent of brain edema and the infarct volume, alleviated neurological deficits, markedly attenuated microglial and astrocyte overactivation, and increased neuronal proliferation and vascular growth. Bioinformatics analysis revealed that BMSCs loaded in composite scaffolds could decrease the level of exosomal miR-206–3p and consequently increase the activity of the PI3K/AKT signaling pathway. In conclusion, BMSCs loaded in novel composite scaffolds exert obvious neuroprotective effects, attenuating ischemic injury by enhancing angiogenesis and neural regeneration in the brain after ischemic stroke, and these results provide a promising approach for treating CNS diseases in the clinic via cell transplantation.