Extracellular vesicles derived from progenitor cells for the treatment of IVD degeneration: a translational study

Abstract Low back pain (LBP) is a common musculoskeletal problem and represents the leading cause of disability and loss of working ability with a strong impact on patients’quality of life in addition to a critical socioeconomic burden on public health worldwide [1]. In healthy conditions intervertebral disc (IVD) acts as a shock absorber between the vertebrae allowing for flexion-extension, lateral flexion and rotation movements [2]. The most frequent symptoms associated to pathological alterations is LBP which affects more than 80% of the population. With aging, the progressive decline of the disc due to chronic processes such as dehydration, inflammation, ability to resist compressive loads, exhaustion of the endogenous cell population and degradation of the extracellular matrix (ECM) lead to the IVD degeneration (IDD) [3]. Although IDD in many cases is asymptomatic, it may be lead to serious problems also associated with chronic LBP, sciatica, segmental instability, spinal stenosis, hypertrophy or ossification of the facets, peripheral neuropathy and disc herniation or prolapsed [4-6]. However, current approaches to treat IDD are based on conservative or surgical procedures with the aim to relieve pain but are not able to change the natural history of the disease [7]. This thesis aims to illustrate the rationale behind a regenerative cell-free approach for IDD as well as the therapeutic potential of paracrine factors derived from mesenchymal stem cells (MSCs) such as extracellular vesicles (EVs).