Therapeutic effect of induced pluripotent stem cell -derived extracellular vesicles in an in vitro and in vivo osteoarthritis model

• DOI: 10.1016/j.jot.2022.10.004
• Publication Date: 2022-11-08T09:51:13Z
• Authors: Yu-Huan Hsueh; Waradee Buddhakosai; Phung Ngan Le; Yung-Yi Tu; Hsien-Chang Huang; Huai-En Lu; Wen-Liang Chen; Yuan-Kun Tu
• Keywords: Viability assay

Osteoarthritis (OA) is a multifactorial joint disease associated with the deterioration of chondrocytes and inflammation. Treatment OA only aimed at reducing pain improving function. Recently, extracellular vesicles (EVs) secreted from stem cells have emerged as cell regenerative tool in several degenerative diseases, including OA. We hypothesised that induced pluripotent (iPSC)-derived EVs would be beneficial for regenerating therapy. Therefore, we to investigate iPSC-EVs' effects on chondrocyte behaviour an interleukin 1 beta (IL-1β)-induced vitro model anterior cruciate ligament transection (ACLT)-induced vivo rabbit articular cartilage.The iPSC-EVs were isolated by sequential ultracentrifugation 48-h-incubated conditional medium iPSC. The characterised transmission electron microscopy, western blot analyses, dynamic light scatter. viability human primary senescence analysed. Premature was long-term incubation low doses hydrogen peroxide. To therapeutic effect vitro, IL-1β used induce damage. Inflammatory macrophages activated THP-1 monocytes observe impact iPSC-EV macrophage polarisation. phenotypes exposed evaluated ELISA analyses. co-cultured different expression collagen II catabolic enzymes chondrocytes. injected intraarticularly into ACLT-induced model. progression lesions assessed through macroscopic histopathological studies.We showed significantly stimulated proliferation suppressed regulating p21 II. reduced matrix degradation IL-6 attenuated IL-1β-mediated death Furthermore, modulated polarisation, resulting rescue damaged inflammatory microenvironment. In ACLT model, OA-like lesions, inflammation, subchondral bone protrusion, cartilage destruction, ameliorated iPSC-EV. A study consistently revealed ACLT-mediated alteration MMP13 ADAMTS5 expression.iPSC-EVs protected enhancing proliferation, suppressing premature senescence, maintaining homeostasis synthesis such metalloproteinases (MMPs) ADAMTS5. also injection indicated upregulation down-regulation Overall, our results suggest possess potential may treatment option.This highlights option regeneration treatment.