Hypoxic culture of umbilical cord mesenchymal stem cell-derived sEVs prompts peripheral nerve injury repair

In the 1980s, exosomes were described as vesicles of endosomal origin secreted from reticulocytes. Interest increased around these extracellular vesicles, as they appeared to participate in several cellular processes. Exosomes bear proteins, lipids, and RNAs, mediating intercellular communication between different cell types in the body, and thus affecting normal and pathological conditions. Only recently, scientists acknowledged the difficulty of separating exosomes from other types of extracellular vesicles, which precludes a clear attribution of a particular function to the different types of secreted vesicles. To shed light into this complex but expanding field of science, this review focuses on the definition of exosomes and other secreted extracellular vesicles. Their biogenesis, their secretion, and their subsequent fate are discussed, as their functions rely on these important processes.

Lipids are essential components of exosomal membranes, and it is well-known that specific lipids are enriched in exosomes compared to their parent cells. In this review we discuss current knowledge about the lipid composition of exosomes. We compare published data for different lipid classes in exosomes, and what is known about their lipid species, i.e. lipid molecules with different fatty acyl groups. Moreover, we elaborate on the hypothesis about hand-shaking between the very-long-chain sphingolipids in the outer leaflet and PS 18:0/18:1 in the inner leaflet, and we propose this to be an important mechanism in membrane biology, not only for exosomes. The similarity between the lipid composition of exosomes, HIV particles, and detergent resistant membranes, used as lipid rafts models, is also discussed. Furthermore, we summarize knowledge about the role of specific lipids and lipid metabolizing enzymes on the formation and release of exosomes. Finally, the use of exosomal lipids as biomarkers and how the lipid composition of exosomes may be of importance for researchers aiming to use exosomes as drug delivery vehicles is discussed. In conclusion, we have summarized what is presently known about lipids in exosomes and identified issues that should be taken into consideration in future studies.

Rodents are commonly used to study the pathophysiological mechanisms of pain as studies in humans may be difficult to perform and ethically limited. As pain cannot be directly measured in rodents, many methods that quantify “pain-like” behaviors or nociception have been developed. These behavioral methods can be divided into stimulus-evoked or non-stimulus evoked (spontaneous) nociception, based on whether or not application of an external stimulus is used to elicit a withdrawal response. Stimulus-evoked methods, which include manual and electronic von Frey, Randall-Selitto and the Hargreaves test, were the first to be developed and continue to be in widespread use. However, concerns over the clinical translatability of stimulus-evoked nociception in recent years has led to the development and increasing implementation of non-stimulus evoked methods, such as grimace scales, burrowing, weight bearing and gait analysis. This review article provides an overview, as well as discussion of the advantages and disadvantages of the most commonly used behavioral methods of stimulus-evoked and non-stimulus-evoked nociception used in rodents.