“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). Researchers from CNRS-Université de Lorraine take stock of occurring EV-based treatments for cartilage regeneration according to their healing effects. They focus 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.
Therapeutic effects of natural EV-based therapy for cartilage healing
(A) Various cell sources for generating non-modified EVs. (B) Example of therapeutic cargos for natural EVs conveying proteins (TGFBI), nucleic acids (lnc KLF3-AS1, miR-100-5p), or lipids (SP1). (C) EV therapeutic effects on cartilage injury or OA. ECM, extracellular matrix; EV, extracellular vesicle; iPSC, induced pluripotent stem cell; iMSC, induced pluripotent stem cell-derived mesenchymal stem cell; lncRNA, long non-coding RNA; miR, microRNA; MSC, mesenchymal stem cell; OA, osteoarthritis; S1P, sphingosine-1-phosphate; TGFBI, transforming growth factor β–induced protein.