OBJECTIVE: Osteoarthritis (OA) is characterized by progressive cartilage degeneration and absence of curative therapies. Therefore, more efficient therapies are compellingly needed. Both mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) and Icariin (ICA) are promising for repair of cartilage defect. This study proposes that ICA may be combined to potentiate the cartilage repair capacity of MSC-EVs. MATERIALS AND METHODS: MSC-EVs were isolated from sodium alginate (SA) and hyaluronic acid (HA) composite hydrogel (SA-HA) cell spheroid culture. EVs and ICA were combined in SA-HA hydrogel to test therapeutic efficacy on cartilage defect in vivo. RESULTS: EVs and ICA were synergistic for promoting both proliferation and migration of MSCs and inflammatory chondrocytes. The combination therapy led to strikingly enhanced repair on cartilage defect in rats, with mechanisms involved in the concomitant modulation of both cartilage degradation and synthesis makers. CONCLUSION: The MSC-EVs-ICA/SA-HA hydrogel potentially constitutes a novel therapy for cartilage defect in OA.
Extracellular Vesicles , Mesenchymal Stem Cells , Osteoarthritis , Animals , Rats , Hydrogels/pharmacology , Hyaluronic Acid/pharmacology , Hyaluronic Acid/metabolism , Cartilage , Chondrocytes/metabolism , Osteoarthritis/drug therapy , Regeneration , Extracellular Vesicles/metabolism
The aberrantly up-regulated CDK9 can be targeted for cancer therapy. The CDK inhibitor dinaciclib (Dina) has been found to drastically sensitizes cancer response to TRAIL-expressing extracellular vesicle (EV-T). However, the low selectivity of Dina has limited its application for cancer. We propose that CDK9-targeted siRNA (siCDK9) may be a good alternative to Dina. The siCDK9 molecules were encapsulated into EV-Ts to prepare a complexed nanodrug (siEV-T). It was shown to efficiently suppress CDK9 expression and overcome TRAIL resistance to induce strikingly augmented apoptosis in lung cancer both in vitro and in vivo, with a mechanism related to suppression of both anti-apoptotic factors and nuclear factor-kappa B pathway. Therefore, siEV-T potentially constitutes a novel, highly effective and safe therapy for cancers.
Lung Neoplasms , NF-kappa B , Humans , NF-kappa B/genetics , NF-kappa B/metabolism , Apoptosis , Cell Line, Tumor , RNA, Small Interfering/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , TNF-Related Apoptosis-Inducing Ligand/genetics , TNF-Related Apoptosis-Inducing Ligand/pharmacology , Receptors, TNF-Related Apoptosis-Inducing Ligand/genetics , Cyclin-Dependent Kinase 9/genetics
