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Chiu, Li-Hsuan

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Chiu

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Li-Hsuan

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Chiu, Li-Hsuan

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    Optical imaging of ovarian cancer using a matrix metalloproteinase-3-sensitive near-infrared fluorescent probe
    (Public Library of Science, 2018) Wang, Kuo-Hwa; Wang, Yung-Ming; Chiu, Li-Hsuan; Chen, Tze-Chien; Tsai, Yu-Hui; Zuo, Chun; Chen, Kuan-Chou; Changou, Chun Austin; Lai, Wen-Fu
    Epithelial ovarian cancer (EOC) is the seventh most common cancer among women worldwide. The 5-year survival rate for women with EOC is only 30%-50%, which is largely due to the typically late diagnosis of this condition. EOC is difficult to detect in its early stage because of its asymptomatic nature. Recently, near-infrared fluorescent (NIRF) imaging has been developed as a potential tool for detecting EOC at the molecular level. In this study, a NIRF-sensitive probe was designed to detect matrix metalloproteinase (MMP) activity in ovarian cancer cells. A cyanine fluorochrome was conjugated to the amino terminus of a peptide substrate with enzymatic specificity for MMP-3. To analyze the novel MMP-3 probe, an in vivo EOC model was established by subcutaneously implanting SKOV3 cells, a serous-type EOC cell line, in mice. This novel MMP-3-sensitive probe specifically reacted with only the active MMP-3 enzyme, resulting in a significantly enhanced NIRF emission intensity. Histological analysis demonstrated that MMP-3 expression and activity were enhanced in the stromal cells surrounding the ovarian cancer cells. These studies establish a molecular imaging reporter for diagnosing early-stage EOC. Additional studies are required to confirm the early-stage activity of MMP-3 in EOC and its diagnostic and prognostic significance.
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    Histological and Immunohistochemical Analyses of Repair of the Disc in the Rabbit Temporomandibular Joint Using a Collagen Template
    (MDPI, 2017) Wang, Kuo-Hwa; Chan, Wing P.; Chiu, Li-Hsuan; Tsai, Yu-Hui; Fang, Chia-Lang; Yang, Charn-Bing; Chen, Kuan-Chou; Tsai, Hung-Li; Lai, Wen-Fu
    A previous study demonstrated that the reconstituted type I collagen matrix extracted from rabbit tendons enabled the TMJ disc to regenerate in the rabbit. The aim of this study was to investigate changes in the extracellular matrix (ECM) and mechanisms of regeneration in the TMJ disc. In 36 New Zealand rabbits that underwent a partial discectomy, discs were replaced with reconstituted collagen templates for 3 months. A histological analysis showed that moderate to severe degeneration appeared in partially discectomized joints without implantation. In contrast, discs experienced regeneration of reconstituted collagen template implantation and the joint returned to normal function. Cells in the regenerative tissue expressed ECM, and fibers became regular and compact due to tissue remodeling over time. Reparative cells differentiated into chondroblasts, and showed highly dense pericellular fibers. The morphology and collagen composition of the disc and condyle in the 3-month experimental group were similar to those of normal tissues. In conclusion, the reconstituted collagen template facilitated the regeneration of surgically discectomized discs. Type I and type II collagens play a crucial role in the regeneration of articular discs.
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    Effects of collagen matrix and bioreactor cultivation on cartilage regeneration of a full-thickness critical-size knee joint cartilage defects with subchondral bone damage in a rabbit model
    (Public Library of Science, 2018) Wang, Kuo-Hwa; Wan, Richard; Chiu, Li-Hsuan; Tsai, Yu-Hui; Fang, Chia-Lang; Bowley, John; Chen, Kuan-Chou; Shih, Hsin-Nung; Lai, Wen-Fu
    Cartilage has limited self-repair ability. The purpose of this study was to investigate the effects of different species of collagen-engineered neocartilage for the treatment of critical-size defects in the articular joint in a rabbit model. Type II and I collagen obtained from rabbits and rats was mixed to form a scaffold. The type II/I collagen scaffold was then mixed with rabbit chondrocytes to biofabricate neocartilage constructs using a rotating cell culture system [three-dimensional (3D)-bioreactor]. The rabbit chondrocytes were mixed with rabbit collagen scaffold and rat collagen scaffold to form neoRBT (neo-rabbit cartilage) and neoRAT (neo-rat cartilage) constructs, respectively. The neocartilage matrix constructs were implanted into surgically created defects in rabbit knee chondyles, and histological examinations were performed after 2 and 3 months. Cartilage-like lacunae formation surrounding the chondrocytes was noted in the cell cultures. After 3 months, both the neoRBT and neoRAT groups showed cartilage-like repair tissue covering the 5-mm circular, 4-mm-deep defects that were created in the rabbit condyle and filled with neocartilage plugs. Reparative chondrocytes were aligned as apparent clusters in both the neoRAT and neoRBT groups. Both neoRBT and neoRAT cartilage repair demonstrated integration with healthy adjacent tissue; however, more integration was obtained using the neoRAT cartilage. Our data indicate that different species of type II/I collagen matrix and 3D bioreactor cultivation can facilitate cartilage engineering in vitro for the repair of critical-size defect.