Mesenchymal Stem Cell-Derived Exosomes: The New Frontier for the Treatment of Intervertebral Disc Degeneration

Abstract

Low back pain (LBP) is one of the most frequent symptoms associated with intervertebral disc degeneration (IDD) and affects more than 80% of the population, with strong psychosocial and economic impacts. The main cause of IDD is a reduction in the proteoglycan content within the nucleus pulposus (NP), eventually leading to the loss of disc hydration, microarchitecture, biochemical and mechanical properties. The use of mesenchymal stem cells (MSCs) has recently arisen as a promising therapy for IDD. According to numerous reports, MSCs mediate their regenerative and immunomodulatory effects mainly through paracrine mechanisms. Recent studies have suggested that extracellular vesicles (EVs) extracted from MSCs may be a promising alternative to cell therapy in regenerative medicine. EVs, including exosomes and microvesicles, are secreted by almost all cell types and have a fundamental role in intercellular communication. Early results have demonstrated the therapeutic potential of MSCs-derived EVs for the treatment of IDD through the promotion of tissue regeneration, cell proliferation, reduction in apoptosis and modulation of the inflammatory response. The aim of this review is to focus on the biological properties, function, and regulatory properties of different signaling pathways of MSCs-derived exosomes, highlighting their potential applicability as an alternative cell-free therapy for IDD.

Wharton's Jelly mesenchymal stromal cell‐derived extracellular vesicles promote nucleus pulposus cell anabolism in an in vitro 3D alginate‐bead culture model

“…Moreover, the EV cargo reflects the pathophysiological state of the donor cell, therefore consequently modulating target cell response. 31 In our study, treatment with three different WJ-MSC-EV concentrations promoted the viability of hNPCs encapsulated in alginate beads after 24 h as well as proliferation at 10 and 14 days following exposure to low (10 μg/mL) and intermediate (50 μg/mL) EV doses.…”

“…Among secreted factors, EVs have attracted particular attention due to their role as messengers and delivery systems between cells. Moreover, the EV cargo reflects the pathophysiological state of the donor cell, therefore consequently modulating target cell response 31 …”

Mesenchymal stem cell-derived secretome enhances nucleus pulposus cell metabolism and modulates extracellular matrix gene expression in vitro

“…Furthermore, factors cointained in MSC secretomes also include EVs, which are involved in cellular communication due to their ability to transport proteins, lipids, and especially nucleic acids. Indeed, EVs can be chemically or biologically modified and selective exosomal mRNAs may “reprogram” target cells by altering or enhancing their physiological state ( Tilotta et al, 2021 ). According to our Live/Dead assay, BM-MSCsec and ADSC-sec were able to increase hNPC viability and decrease cell death compared to the control group.…”

Editorial: Immunological imbalance: What is its role in intervertebral disc degeneration?

“…On the side of the review in this Research Topic, we are happy to have received this very detailed study by Li et al on the description of extracellular vesicles (EVs) and their potential role for IVD repair. This study can be recommended for researchers interested in the fast growing field along with another important review that were recently published on EVs and the field of IVD repair and regeneration ( Li et al ; Tilotta et al, 2021 ).…”