Purified Exosome Product Enhances Chondrocyte Survival and Regeneration by Modulating Inflammation and Promoting Chondrogenesis

Abstract

Aim: This study was to detect the effects of purified exosome product (PEP) on C28/I2 cells and chondrocytes derived from osteoarthritis patients. Materials & methods: Cell viability and apoptosis assays were used to detect the effect of PEP on cells. qRT-PCR and cell fluorescence assays were used to investigate the potential mechanism of PEP on cell chondrogenesis. Results: PEP was internalized by cells at a fast rate and enhanced cellular proliferation and migration while attenuating apoptosis. These findings reflect the fact that PEP can increase the expression of PCNA and reduce the expression of CASP3/ 7/ 9 and BAX. Conclusion: This study suggests an innovative strategy for chondrogenesis that could be applied to osteoarthritis repair in the future.

Dose–response analysis after administration of a human platelet‐derived exosome product on neurite outgrowth in vitro

“…While the neuroregenerative effect of exosomes has recently been highlighted and their application in tissue regeneration (i.e., bone, wound, and tendon) has been increasingly investigated, little is known about the mechanisms of action of exosomes (Ikumi et al, 2021;Kisby et al, 2021;Ren et al, 2021;Shi et al, 2021Shi et al, , 2023Wellings et al, 2021). In this study, a PEP dose-response analysis was successfully investigated and examined effects of neurite outgrowth in vitro.…”

“…The exosomes are lyophilized and stored as a stabilized powder cake in glass vials at RT. PEP may have a great potential to enhance tissue repair and regeneration (Ikumi et al, 2021;Kisby et al, 2021;Ren et al, 2021;Shi et al, 2021Shi et al, , 2023Wellings et al, 2021) protein-1, hepatocyte growth factor, and vascular endothelial growth factor (Ikumi et al, 2021). Peripheral nerve basic science research using MSCs has been greatly studied over the past decades.…”

“…Concentrations higher than the optimal dosage may provoke the negative feedback loop resulting in a decreased effect by stimulating nonspecific ligands without beneficial effects (Acuto et al, 2008; Dimmitt & Stampfer, 2009; Kholodenko et al, 2021; Stolyarova et al, 2014). The proregenerative effect of PEP counter‐balanced by regulatory signaling mechanisms is thought to be inherent to cells and tissues, as this saturation effect of PEP is found across many cell and tissue types (Shi et al, 2023). Therefore, this effect is postulated to be observed similarly when translating to three‐dimensional (3D) in vitro or in vivo models.…”

Reconstituted Extracellular Vesicles from Human Platelets Decrease Viral Myocarditis in Mice

“…Mice (8-10 per group) were inoculated intraperitoneally (ip) with 10 3 plaque-forming units (PFUs) of heart-passaged stock of CVB3 on day 0, and myocarditis examined at day 10 or 35 pi. [109,110] CVB3 (Nancy strain) was obtained from the American Type Culture Collection (ATCC; Manassas, VA, USA) and grown in Vero cells (ATCC) to create a tissueculture-derived virus stock. [65] 100 μL of tissue culture virus (10 3 PFU) was injected ip into 4 week old female BALB/c mice and virus obtained from hearts at day 3 pi by homogenization in Gibco Minimum Essential Media (Thermo-Scientific, Waltham, MA, USA, 11095-080) supplemented with 2% heat-inactivated fetal bovine serum (FBS).…”

“…PEV was reconstituted in sterile PBS to obtain a final concentration of 11.2 mg dry weight PEV mL −1 or 16.67% PEV which contained 1.2 × 10 12 EVs per vial, as previously described. [109,110] EV Characterization: The size distribution and particle concentration of reconstituted PEV were characterized with NTA, as described previously. [113,124] PEV was reconstituted and diluted 1:100 in PBS and analyzed with a Nanosight NS300 V3.3.4 (Malvern Panalytical, Malvern, UK), using the following measurement settings: three replicates with measurement time at 60 s, flow rate 40 μL min −1 , camera level 11, and detection threshold 4.…”