Needle-Free Injection of Exosomes Derived from Human Dermal Fibroblast Spheroids Ameliorates Skin Photoaging
ACS NANO
Authors: Hu, Shiqi; Li, Zhenhua; Cores, Jhon; Huang, Ke; Su, Teng; Phuong-Uyen Dinh; Cheng, Ke
Abstract
Human dermal fibroblasts (HDFs), the main cell population of the dermis, gradually lose their ability to produce collagen and renew intercellular matrix with aging. One clinical application for the autologous trans-dermis injection of HDFs that has been approved by the Food and Drug Administration aims to refine facial contours and slow down skin aging. However, the autologous HDFs used vary in quality according to the state of patients and due to many passages they undergo during expansion. In this study, factors and exosomes derived from three-dimensional spheroids (3D HDF-XOs) and the monolayer culture of HDFs (2D HDF-XOs) were collected and compared. 3D HDF-XOs expressed a significantly higher level of tissue inhibitor of metalloproteinases-1 (TIMP-1) and differentially expressed miRNA cargos compared with 2D HDF-XOs. Next, the efficacy of 3D HDF-XOs in inducing collagen synthesis and antiaging was demonstrated in vitro and in a nude mouse photoaging model. A needle-free injector was used to administer exosome treatments. 3D HDF-XOs caused increased procollagen type I expression and a significant decrease in MMP-1 expression, mainly through the downregulation of tumor necrosis factor-alpha (TNF-alpha) and the upregulation of transforming growth factor beta (TGF-beta). In addition, the 3D-HDF-XOs group showed a higher level of dermal collagen deposition than bone marrow mesenchymal stem cell-derived exosomes. These results indicate that exosomes from 3D cultured HDF spheroids have anti-skin-aging properties and the potential to prevent and treat cutaneous aging.
Verification of Saliva Matrix Metalloproteinase-1 as a Strong Diagnostic Marker of Oral Cavity Cancer
CANCERS
Authors: Chang, Ya-Ting; Chu, Lichieh Julie; Liu, Yen-Chun; Chen, Chih-Jou; Wu, Shu-Fang; Chen, Chien-Hua; Chang, Ian Yi-Feng; Wang, Jun-Sheng; Wu, Tzong-Yuan; Dash, Srinivas; Chiang, Wei-Fan; Chiu, Sheng-Fu; Gou, Shin-Bin; Chien, Chih-Yen; Chang, Kai-Ping; Yu, Jau-Song
Abstract
Oral squamous cell carcinoma (OSCC) accounts for >90% of cases of oral cancer, including cancer at the lip and oral cavity and cancer at the oropharynx. Most OSCCs develop from oral potentially malignant disorders (OPMDs), which consist of heterogeneous lesions with different malignant transformation potentials that make early detection of OSCC a challenge. Using a targeted mass spectrometry-based assay to compare multiple candidate proteins, we previously identified matrix metalloproteinase-1 (MMP-1) as one of the most promising salivary OSCC biomarkers. To explore the clinical utility of MMP-1 in OSCC detection, we developed an in-house, sensitive enzyme-linked immunosorbent assay (ELISA) for measuring MMP-1 content, and tested it on saliva samples from 1160 subjects (313 healthy controls, and 578 OPMD and 269 OSCC patients) collected at two medical centers. Salivary MMP-1 levels measured by our in-house ELISA significantly discriminated OSCC patients from non-cancerous groups. A receiver operating characteristic curve analysis showed that MMP-1 was effective in separating non-cancer groups from patients with OSCCs at the oral cavity. Additionally, salivary MMP-1 levels in oral cavity cancer patients were highly correlated with tumor progression (tumor size, lymph node metastasis, and overall stage). Collectively, our results indicate that salivary MMP-1 is an effective biomarker for OSCC that can be sensitively detected using our newly developed ELISA. The newly developed MMP-1 ELISA may be used as a new adjunctive tool to aid in detecting and monitoring OSCC.