Extracellular Vesicles: An Emerging Clinical Opportunity in Musculoskeletal Disease.

Extracellular vesicles (EVs) are important mediators of cell-to-cell communication in the extracellular space. These membranous nanoparticles carry various molecules, often referred to as "cargo," which are delivered to nearby target cells. In the past decade, developments in nanotechnology have allowed for various new laboratory techniques for the increased utilization of EVs in cellular and animal studies. Such techniques have evolved for the isolation, characterization, and delivery of EVs to biological tissues. This emerging technology has immense clinical potential for both diagnostic and therapeutic applications. Various EV cargo molecules, including DNA, RNA, and proteins, can act as pathological biomarkers. Furthermore, EVs derived from certain cell sources have shown therapeutic benefit in certain pathologies. In addition to their native therapeutic benefit, EVs can be engineered to carry and selectively deliver therapeutic agents. While EVs have gained increasing interest in various pathologies, few studies have compiled their clinical potential in musculoskeletal pathologies. To bridge this gap, we present an overview of EVs, introduce current laboratory preparation techniques, and outline the most recent literature regarding the potential therapeutic applications of EVs in musculoskeletal pathologies.

Cortical regulation of neurogenesis and cell proliferation in the ventral subventricular zone.

Neurogenesis and differentiation of neural stem cells (NSCs) are controlled by cell-intrinsic molecular pathways that interact with extrinsic signaling cues. In this study, we identify a circuit that regulates neurogenesis and cell proliferation in the lateral ventricle-subventricular zone (LV-SVZ). Our results demonstrate that direct glutamatergic projections from the anterior cingulate cortex (ACC), as well as inhibitory projections from calretinin+ local interneurons, modulate the activity of cholinergic neurons in the subependymal zone (subep-ChAT+). Furthermore, in vivo optogenetic stimulation and inhibition of the ACC-subep-ChAT+ circuit are sufficient to control neurogenesis in the ventral SVZ. Both subep-ChAT+ and local calretinin+ neurons play critical roles in regulating ventral SVZ neurogenesis and LV-SVZ cell proliferation.