Abstract
“Extracellular vesicles” (EVs) is a term gathering biological particles released from cells that act as messengers for cell-to-cell communication. Like cells, EVs have a membrane with a lipid bilayer, but unlike these latter, they have no nucleus and consequently cannot replicate. Several EV subtypes (e.g., exosomes, microvesicles) are described in the literature. However, the remaining lack of consensus on their specific markers prevents sometimes the full knowledge of their biogenesis pathway, causing the authors to focus on their biological effects and not their origins. EV signals depend on their cargo, which can be naturally sourced or altered (e.g., cell engineering). The ability for regeneration of adult articular cartilage is limited because this avascular tissue is partly made of chondrocytes with a poor proliferation rate and migration capacity. Mesenchymal stem cells (MSCs) had been extensively used in numerous in vitro and preclinical animal models for cartilage regeneration, and it has been demonstrated that their therapeutic effects are due to paracrine mechanisms involving EVs. Hence, using MSC-derived EVs as cell-free therapy tools has become a new therapeutic approach to improve regenerative medicine. EV-based therapy seems to show similar cartilage regenerative potential compared with stem cell transplantation without the associated hindrances (e.g., chromosomal aberrations, immunogenicity). The aim of this short review is to take stock of occurring EV-based treatments for cartilage regeneration according to their healing effects. The article focuses on cartilage regeneration through various sources used to isolate EVs (mature or stem cells among others) and beneficial effects depending on cargos produced from natural or tuned EVs.
Highlights
With an aging population, musculoskeletal diseases remain a worldwide challenge, both economical and therapeutic, for public health (Woolf and Pfleger, 2003; Sanchez-Adams et al, 2014; Hunter and Bierma-Zeinstra, 2019)
Ruiz et al (2020), showed that TGBI silencing inhibits murine bone marrow–derived MSCs (BMMSCs)’ chondroinductive effect in vitro and healing effect in a collagenase-induced OA mouse model. These positive effects are due to the presence of TGF-BI mRNA and protein in BMMSC-derived extracellular vesicles (EVs), suggesting that TGF-BI is a new key factor released by Mesenchymal stem cells (MSCs) to protect cartilage and favor its anabolism (Ruiz et al, 2020)
EVs secreted by human iPSC-derived MSCs (iMSCs) alleviate OA in the mouse, in vitro in chondrocytes treated with interleukin 1β (IL-1β) and in vivo by limiting cartilage destruction and matrix degradation according to Osteoarthritis Research Society International (OARSI) scores in a model based on knee joint instability induced by surgery (Wang et al, 2017)
Summary
Musculoskeletal diseases remain a worldwide challenge, both economical and therapeutic, for public health (Woolf and Pfleger, 2003; Sanchez-Adams et al, 2014; Hunter and Bierma-Zeinstra, 2019). All these benefits offer new insights to use EVs as regenerative medicine tools to heal cartilage This mini review summarizes current EV-based treatments to improve cartilage degeneration by focusing on various sources to produce EVs and the positive effects of the therapeutic cargos from natural or modified EVs. EVs participate in the modulation of numerous cell regulatory processes (e.g., proliferation, differentiation, or inflammation), making these membranous entities perfect stakeholders for tissue regeneration according to their various sources (Dostert et al, 2017; Tsiapalis and O’Driscoll, 2020). There is only one clinical trial involving EVs to treat cartilage injury It is based on the promising results from Niada et al (2019), where MSCs derived from adipose tissue of healthy donors undergoing aesthetic or prosthetic surgery. Kouroupis et al (2019) showed that primed MSCs derived from the IFP exhibit enhanced immunomodulatory properties in vitro and in vivo (Figures 1A,C)
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