A Comparative Study on the Effect of Exosomes Secreted by Mesenchymal Stem Cells Derived from Adipose and Bone Marrow Tissues in the Treatment of Osteoarthritis-Induced Mouse Model

Abstract

Background. Exosomes as extracellular vesicles (EVs) are nanoscale intercellular messengers secreted from cells to deliver biological signals. Today, exosomes have become a new field of research in regenerative medicine and are considered as potential therapies to control inflammation and wound healing and enhance and improve healing in many diseases. Given the global burden of osteoarthritis (OA) as the fastest-growing health condition and one of the major causes of physical disability in the aging population, research to establish EVs as therapeutic products can meet the basic clinical needs in the management of osteoarthritis and provide a therapeutic solution. Objectives. The present study is aimed at evaluating the regenerative potentials of the exosomes secreted from adipose and bone marrow tissue-derived mesenchymal stem cells (AD- and BM-MSCs) in ameliorating the symptoms of OA. Method. In this experimental study, AD- and BM-MSCs were isolated and cultured in the laboratory until passage 3. Finally, these cells’ secreted exosomes were isolated from their conditioned medium. Ciprofloxacin-induced OA mouse models underwent intra-articular injection of exosomes from AD-MSCs and BM-MSCs. Finally, the expression levels of collagen I and II, sox9, and aggrecan genes using real-time PCR, histological analysis, and immunohistochemical (IHC) studies were performed. Results. Real-time PCR data showed that although the expression level of collagen type II was lower in both exosome-treated groups than the normal, but it was significantly increased in comparison with the sham and OA, with higher expression in BM-Exo rather than AD-Exo group. Similarly, the histological staining and IHC results have provided almost identical data, emphasizing on better therapeutic effect of BM-MSCs-exosome than AD-MSCs-exosome. Conclusion. BM-MSCs secreted exosomes in comparison with AD-MSCs could be considered as a better therapeutic option to improve osteoarthritis and exhibit potential as a disease-modifying osteoarthritis cell-free product.

3D Spheroid Cultures of Stem Cells and Exosome Applications for Cartilage Repair

“…COLII is the most common type of hyaline found in all cartilage tissues, and it is responsible for the stability and biological functions of healthy articular cartilage [ 82 ]. Fazaeli et al [ 78 ] showed that while COLII expression was lower in both exosome-treated groups than in the control group, it was significantly higher in the sham and OA groups, with a higher expression in the bone-marrow-exosome group than in the adipose-tissue-exosome group. Cosenza et al [ 76 ] found that injecting MSC-derived exosomes into the articular cavity protected mice from OA.…”

Human bone marrow mesenchymal stem cell-derived extracellular vesicles inhibit shoulder stiffness via let-7a/Tgfbr1 axis

“…Recently, two studies have compared the therapeutic effects of BMSC-EVs and AMSC-EVs. Fazaeli et al found that BMSC-EVs could result in better outcomes for osteoarthritis than AMSC-EVs [ 36 ]. Through miRNAs sequencing and the bioinformatic analysis, Pomatto et al reported that BMSC-EVs could promote more robust cell viability than AMSC-EVs [ 37 ].…”

Intra-Articular Injection of Adipose-Derived Stem Cells Ameliorates Pain and Cartilage Anabolism/Catabolism in Osteoarthritis: Preclinical and Clinical Evidences

“…Our in vivo data from OA rat model also showed statistically significant improvement in histopathological staining, pain behavior, which were in consistent with previous animal researches. Apart from the direct incorporation of ADSCs, recent studies have suggested that the paracrine effect of ADSCs played an important role in treating OA ( Fazaeli et al, 2021 ; Zuxiang Chen et al, 2021 ). Our results also suggested that paracrine molecules of ADSCs exerted the anti-OA effect.…”