The mammalian circadian and sleep-wake systems are closely aligned through their coordinated regulation of daily activity patterns. Although they differ in their anatomical organization and physiological processes, they utilize overlapping regulatory mechanisms that include an assortment of proteins and molecules interacting within the extracellular space. These extracellular factors include proteases that interact with soluble proteins, membrane-attached receptors and the extracellular matrix; and cell adhesion molecules that can form complex scaffolds connecting adjacent neurons, astrocytes and their respective intracellular cytoskeletal elements. Astrocytes also participate in the dynamic regulation of both systems through modulating neuronal appositions, the extracellular space and/or through release of gliotransmitters that can further contribute to the extracellular signaling processes. Together, these extracellular elements create a system that integrates rapid neurotransmitter signaling across longer time scales and thereby adjust neuronal signaling to reflect the daily fluctuations fundamental to both systems. Here we review what is known about these extracellular processes, focusing specifically on areas of overlap between the two systems. We also highlight questions that still need to be addressed. Although we know many of the extracellular players, far more research is needed to understand the mechanisms through which they modulate the circadian and sleep-wake systems.

Over the past few decades, there has been growing interest in understanding the molecular mechanisms of cancer pathogenesis and progression, as it is still associated with high morbidity and mortality. Current management of large bone sarcomas typically includes the complex therapeutic approach of limb salvage or sacrifice combined with pre- and postoperative multidrug chemotherapy and/or radiotherapy, and is still associated with high recurrence rates. The development of cellular strategies against specific characteristics of tumour cells appears to be promising, as they can target cancer cells selectively. Recently, Mesenchymal Stromal Cells (MSCs) have been the subject of significant research in orthopaedic clinical practice through their use in regenerative medicine. Further research has been directed at the use of MSCs for more personalized bone sarcoma treatments, taking advantage of their wide range of potential biological functions, which can be augmented by using tissue engineering approaches to promote healing of large defects. In this review, we explore the use of MSCs in bone sarcoma treatment, by analyzing MSCs and tumour cell interactions, transduction of MSCs to target sarcoma, and their clinical applications on humans concerning bone regeneration after bone sarcoma extraction.