Matrix-Bound Nanovesicles: What Are They and What Do They Do?

Over the past 50 years, several different types of extracellular vesicles have been discovered including exosomes, microvesicles, and matrix vesicles. These vesicles are secreted by cells for specific purposes and contain cargo such as microRNA, cytokines, and lipids. A novel extracellular vesicle, the matrix-bound nanovesicle (MBV), has been recently discovered. The MBV is similar to the microvesicle, however, it is attached to the extracellular matrix, instead of being secreted. This review compares MBVs to other types of extracellular vesicles to try and better understand their origin and function. Further, this review will explain various extracellular vesicle isolation methods and how these can be used for MBVs and summarize characterization of MBV cargo such as microRNA, proteins, and lipids. Lastly, we will summarize the effects of MBVs on cells. MBVs are a novel class of extracellular vesicles that hold great promise as a platform for delivery of targeted gene and drug therapeutics.

Injectable decellularized nucleus pulposus tissue exhibits neuroinhibitory properties.

Background: Chronic low back pain (LBP) is a leading cause of disability, but treatments for LBP are limited. Degeneration of the intervertebral disc due to loss of neuroinhibitory sulfated glycosaminoglycans (sGAGs) allows nerves from dorsal root ganglia to grow into the core of the disc. Treatment with a decellularized tissue hydrogel that contains sGAGs may inhibit nerve growth and prevent disc-associated LBP. Methods: A protocol to decellularize porcine nucleus pulposus (NP) was adapted from previous methods. DNA, sGAG, α-gal antigen, and collagen content were analyzed before and after decellularization. The decellularized tissue was then enzymatically modified to be injectable and form a gel at 37°C. Following this, the mechanical properties, microstructure, cytotoxicity, and neuroinhibitory properties were analyzed. Results: The decellularization process removed 99% of DNA and maintained 74% of sGAGs and 154% of collagen compared to the controls NPs. Rheology demonstrated that regelled NP exhibited properties similar to but slightly lower than collagen-matched controls. Culture of NP cells in the regelled NP demonstrated an increase in metabolic activity and DNA content over 7 days. The collagen content of the regelled NP stayed relatively constant over 7 days. Analysis of the neuroinhibitory properties demonstrated regelled NP significantly inhibited neuronal growth compared to collagen controls. Conclusions: The decellularization process developed here for porcine NP tissue was able to remove the antigenic material while maintaining the sGAG and collagen. This decellularized tissue was then able to be modified into a thermally forming gel that maintained the viability of cells and demonstrated robust neuroinhibitory properties in vitro. This biomaterial holds promise as an NP supplement to prevent nerve growth into the native disc and NP in vivo.