Is Extracellular Vesicle-Based Therapy the Next Answer for Cartilage Regeneration?

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.

Bone Marrow MSC Secretome Increases Equine Articular Chondrocyte Collagen Accumulation and Their Migratory Capacities

“…The MSC secretome is composed of a wide variety of molecules. Nevertheless, since it has already been demonstrated that EVs derived from MSCs were able to enhance chondrocyte proliferation, delay experimentally induced OA, and even repair cartilage [ 6 ], we hypothesized that equine MSC-derived EVs could participate in the effect we observed with eACs. The size and concentration of nanoparticles included in MSC-CM were assessed by nanoparticle tracking analysis (NTA).…”

“…A future study of the MSC-CM vesiculome, comprising EVs secreted by MSCs, could confirm our hypothesis. Indeed, several works in small mammal models have demonstrated that EVs derived from multipotent stem cells were able to enhance chondrocyte proliferation, delay experimentally induced OA, and even restore cartilage [ 6 ]. Additionally, EVs can have an equivalent or even a superior effect than the cell type they derive.…”

“…Among stem cells, the differentiation of adult mesenchymal stem cells (MSCs) into chondrocytes is an attractive approach but has some limitations, notably, their incomplete differentiation status which can generally be improved. Beyond their differentiation capacities, MSCs are able to secrete a large variety of soluble mediators and extracellular vesicles (EVs), known as the cell secretome, which participates in their most relevant physiological functions, including tissue repair and immunomodulation [ 5 , 6 ]. Indeed, several in vivo studies have shown that intra-articular injections of MSCs can promote the repair of chondral defects and/or reduce inflammation [ 7 , 8 , 9 , 10 , 11 ].…”

Extra-cellular vesicles of the male genital tract: new actors in male fertility?

“…Indeed, tissue regeneration relies on healing factors carried by EVs to generate a trophic microenvironment suitable for diseases. EVs can be untouched and used as therapeutic agents in their regular or natural state after isolation from biological samples or conditioned medium in standard cell culture conditions [ 62 ]. There is still a need for a consensus concerning EV isolation methods and EV characterization/designation remains.…”

Therapeutic Strategy of Mesenchymal-Stem-Cell-Derived Extracellular Vesicles as Regenerative Medicine

“…Extracellular vesicles (EVs), which are nano- to micro-sized lipid bilayer membrane particles secreted by host cells, play critical roles in novel intercellular communication mechanisms, mediating the transduction of functional molecules with physiological activity, such as microRNAs, mRNAs, proteins, and lipids ( Figure 1 ) [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ,…”