Bio-hybrid artificial organs are an attractive concept to restore organ function through precise biological cooperation with surrounding tissues in vivo. However, in bio-hybrid artificial organs, an artificial organ with fibrous connective tissues, including muscles, tendons and ligaments, has not been developed. Here, we have enveloped with embryonic dental follicle tissue around a HA-coated dental implant, and transplanted into the lower first molar region of a murine tooth-loss model. We successfully developed a novel fibrous connected tooth implant using a HA-coated dental implant and dental follicle stem cells as a bio-hybrid organ. This bio-hybrid implant restored physiological functions, including bone remodelling, regeneration of severe bone-defect and responsiveness to noxious stimuli, through regeneration with periodontal tissues, such as periodontal ligament and cementum. Thus, this study represents the potential for a next-generation bio-hybrid implant for tooth loss as a future bio-hybrid artificial organ replacement therapy.

A case of sclerosing odontogenic carcinoma (SOC) admixed with a benign fibro-osseous lesion (BFOL) is reported herein. A 67-year-old male had paresthesia in the mental region. Computed tomography detected an intragnathic mass that was focally expansile with disappearance of cortical bone, and contained admixed radiolucency and radio-opacity. Under the pathological diagnosis as benign fibro-osseous lesion, it was surgically removed by curettage. Microscopic analysis showed that a few parts of the resected materials contained dispersed thin cords and small nests of epithelial cells accompanied by fibrous stroma. Cellular atypia and mitotic figures were not evident. The diagnosis of BFOL with hyperplastic and metaplastic odontogenic epithelia was ultimately made. Eight months after the operation, the lesion recurred and segmental mandibulectomy was carried out. Histologically, the lesion was predominantly occupied by the fibro-osseous component with irregular-shaped foci of epithelial component. The epithelial component exhibited mostly thin cord or small nest patterns and showed definite perineural infiltration. Immunohistochemically, the epithelial cells were positive for p63, cytokeratin (CK) 6 and CK19, and focally positive for CK7 but negative for vimentin. MIB-1 positive nuclei were inconspicuous. To the best of our knowledge, this report is the first case of SOC with BFOL.

Lymph node metastasis is a major factor for poor prognosis in oral squamous cell carcinoma (OSCC). However, the molecular mechanisms of lymph node metastasis are unclear. We determined that angiopoietin-like protein 4 (ANGPTL4) mRNA and protein expression were increased in OSCC cells established from the primary site in metastatic cases. In addition, ANGPTL4 expression in biopsy specimens was correlated with the presence of lymph node metastasis. Therefore, our initial findings suggest that OSCC cells expressing ANGPTL4 may possess metastatic ability. Furthermore, cell culture supernatants from OSCC cells that metastasized to the lymph node contain ANGPTL4 and promote invasive ability. These findings suggest that secreted ANGPTL4 may affect the invasive ability of OSCC. Moreover, the rates of positive ANGPTL4 expression at the primary site were significantly higher in the lymph node metastasis group. These results demonstrate that ANGPTL4 contributes to OSCC metastasis by stimulating cell invasion. Therefore, ANGPTL4 is a potential therapeutic target for preventing cancer metastasis.

HPIP may play a critical role in oral carcinogenesis and is thus a potential target for anticancer therapy, with particular emphasis on its involvement in differentiation and migration/metastasis.

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