Cancer is a leading cause of mortality and a major public health problem worldwide. For biological therapy against cancer, we previously developed a unique immunotherapeutic platform by combining mesenchymal stem cells with an antigen-specific protein vaccine. However, this system possesses a few limitations, such as improperly immortalized mesenchymal stem cells (MSCs) along with transfected oncogenic antigens in them. To overcome the limitations of this platform for future clinical application, we freshly prepared primary adipose-derived stem cells (ADSCs) and modified the E7’ antigen (E7’) as a non-oncogenic protein. Either subcutaneously co-inoculated with cancer cells or systemically administered after tumor growth, ADSC labeled with enhanced green fluorescent protein (eGFP) and combined with modified E7’ (ADSC-E7’-eGFP) cells showed significant antitumor activity when combined with the protein vaccine in both colon and lung cancer in mice. Specifically, this combined therapy inhibited tumor through inducing cell apoptosis. The significantly reduced endothelial cell markers, CD31 and vascular endothelial growth factor (VEGF), indicated strongly inhibited tumor angiogenesis. The activated immune system was demonstrated through the response of CD4+ T and natural killer (NK) cells, and a notable antitumor activity might be contributed by CD8+ T cells. Conclusively, these evidences imply that this promising immunotherapeutic platform might be a potential candidate for the future clinical application against cancer.

Besides inhalation, a few studies have indicated that the uptake of nicotine through air or clothing may be a significant pathway of its exposure among passive smokers. Nicotine is well known to exert various physiological impacts, including stimulating sympathetic nervous system, causing vascular disturbances, and inducing cell death. Therefore, we aimed to establish whether exposure of nicotine could induce articular cartilage degeneration in a mouse model of osteoarthritis (OA). We specifically assessed dose-dependent effect of nicotine in vitro to mimic its accumulation. Further, during the in vivo studies, mice subcutaneously administered with nicotine was examined for OA-associated pathologic changes. We found that nicotine significantly suppressed chondrocytes and chondrogenic markers (Sox, Col II, and aggrecan). Nicotine-treated mice also showed altered knee joint ultrastructure with reduced Col II and proteoglycans. After corroborating nicotine-induced OA characteristics, we treated this pathologic condition through employing platelet-derived biomaterial (PDB)-based regenerative therapy. The PDB significantly suppressed OA-like pathophysiological characteristics by 4 weeks. The mechanistic insight underlying this therapy demonstrated that PDB significantly restored levels of insulin-like growth factor 1 (IGF-1) signaling pathway proteins, especially pIGF-1 R, pAKT, and IRS-1, regulating extracellular matrix synthesis by chondrocytes. Taken together, the PDB exerts regenerative and reparative activities in nicotine-mediated initiation and progression of OA, through modulating IGF-1/AKT/IRS-1 signaling axis.