Abstract
The inability of cartilage to self-repair necessitates an effective therapeutic approach to restore damaged tissues. Extracellular vesicles (EVs) are attractive options because of their roles in cellular communication and tissue repair where they regulate the cellular processes of proliferation, differentiation, and recruitment. However, it is a challenge to determine the relevant cell sources for isolation of EVs with high chondrogenic potential. The current study aims to evaluate the chondrogenic potential of EVs derived from chondrocytes (Cho-EV) and mesenchymal stem cells (MSC-EV). The EVs were separately isolated from conditioned media of both rabbit bone marrow MSCs and chondrocyte cultures. The isolated vesicles were assessed in terms of size, morphology, and surface marker expression. The chondrogenic potential of MSCs in the presence of different concentrations of EVs (50, 100, and 150 μg/ml) was evaluated during 21 days, and chondrogenic surface marker expressions were checked by qRT-PCR and histologic assays. The extracted vesicles had a spherical morphology and a size of 44.25 ± 8.89 nm for Cho-EVs and 112.1 ± 10.10 nm for MSC-EVs. Both groups expressed the EV-specific surface markers CD9 and CD81. Higher expression of chondrogenic specified markers, especially collagen type II (COL II), and secretion of glycosaminoglycans (GAGs) and proteoglycans were observed in MSCs treated with 50 and 100 μg/ml MSC-EVs compared to the Cho-EVs. The results from the use of EVs, particularly MSC-EVs, with high chondrogenic ability will provide a basis for developing therapeutic agents for cartilage repair.
Highlights
Articular cartilage (AC) does not have blood vessels and possesses low cell density; even minor injuries can lead to disorders such as osteoarthritis (OA) [1]
alizarin red S (ARS) results confirmed the osteogenic potential of these Mesenchymal Stem Cell (MSC) by the presence of bone-like nodules in the extracellular matrix (ECM) (Figure 1(c), A and B)
Our results demonstrated that extracellular vesicles (EVs) from chondrocytes and MSCs could enhance the chondrogenesis of MSCs in a cell micromass culture that is induced by TGF-beta signaling
Summary
Articular cartilage (AC) does not have blood vessels and possesses low cell density; even minor injuries can lead to disorders such as osteoarthritis (OA) [1]. Administration of extracellular vesicles (EVs) is under consideration as a cell-free and noncellular approach. EVs overcome the challenges attributed to stem cell therapy such as immunogenicity and tumorigenesis [4, 5]. EVs are vesicles that have lipid bilayer membranes, which can be isolated from a variety of cells as well as body fluids such as serum, saliva, cerebrospinal fluid, and synovial fluid [6, 7]. The results of the studies show that the contents of EVs are representative of the cells from which they are isolated
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