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Abstract
Extracellular vesicles (EVs) are lipid membrane particles carrying proteins, lipids, DNA, and various types of RNA that are involved in intercellular communication. EVs derived from mesenchymal stem cells (MSCs) have been investigated extensively in many different fields due to their crucial role as regeneration drivers, but research for their use in degenerative diseases of the intervertebral disc (IVD) has only started recently. MSC-derived EVs not only promote extracellular matrix synthesis and proliferation in IVD cells, but also reduce apoptosis and inflammation, hence having multifunctional beneficial effects that seem to be mediated by specific miRNAs (such as miR-233 and miR-21) within the EVs. Aside from MSC-derived EVs, IVD-derived EVs (e.g., stemming from notochordal cells) also have important functions in IVD health and disease. This article will summarize the current knowledge on MSC-derived and IVD-derived EVs and will highlight areas of future research, including the isolation and analysis of EV subpopulations or exposure of MSCs to cues that may enhance the therapeutic potential of released EVs.
Highlights
Degenerative disc disease (DDD) is a major origin of low back pain, which is the leading cause of activity limitation and work absence and results in a high economic burden (Pai and Sundaram, 2004)
DDD is defined as symptomatic intervertebral disc (IVD) degeneration, whereby nociception is thought to be linked to increased levels of proinflammatory cytokines within the tissue, including IL-1β, TNF-α, IL-6, IL-8, and IFN-γ (Wuertz and Haglund, 2013; Johnson et al, 2015)
As chronic inflammation in the IVD arising from resident cells is associated with back pain development (Wuertz and Haglund, 2013; Johnson et al, 2015), many researchers consider the modulation of inflammation as therapeutically more relevant and achievable than inducing full regeneration
Summary
Degenerative disc disease (DDD) is a major origin of low back pain, which is the leading cause of activity limitation and work absence and results in a high economic burden (Pai and Sundaram, 2004). Various techniques have recently been developed that may promote MSC survival and functionality in the IVD, such as priming and pre-differentiation of MSCs, selection of specific MSC subpopulations, and rewiring of the genetic circuits of MSCs by CRISPR (Krupkova et al, 2018; Loibl et al, 2019), there has been an increasing shift toward cell-free, yet MSC-related therapies to avoid the aforementioned challenges. Conclusions are challenging to draw as dose-effects are difficult to control for in these experimental set-ups This mini-review will briefly summarize both established and more advanced techniques for the collection and size-sorting of EVs before presenting evidence on the content and function of MSC-derived EVs on cells from the inner region of the IVD, the nucleus pulposus (NP). Knowledge on the characterization of EVs released from IVD cells are briefly summarized and future areas of research are highlighted
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