Tooth Germ‐Like Construct Transplantation for Whole‐Tooth Regeneration: An In Vivo Study in the Miniature Pig

The purpose of this study was to demonstrate the feasibility of whole‐tooth regeneration using a tooth germ‐like construct. Dental pulp from upper incisors, canines, premolars, and molars were extracted from sexually mature miniature pigs. Pulp tissues were cultured and expanded in vitro to obtain dental pulp stem cells (DPSCs), and cells were differentiated into odontoblasts and osteoblasts. Epithelial cells were isolated from gingival epithelium. The epithelial cells, odontoblasts, and osteoblasts were seeded onto the surface, upper, and lower layers, respectively, of a bioactive scaffold. The lower first and second molar tooth germs were removed bilaterally and the layered cell/scaffold constructs were transplanted to the mandibular alveolar socket of a pig. At 13.5 months postimplantation, seven of eight pigs developed two teeth with crown, root, and pulp structures. Enamel‐like tissues, dentin, cementum, odontoblasts, and periodontal tissues were found upon histological inspection. The regenerated tooth expressed dentin matrix protein‐1 and osteopontin. All pigs had regenerated molar teeth regardless of the original tooth used to procure the DPSCs. Pigs that had tooth germs removed or who received empty scaffolds did not develop teeth. Although periodontal ligaments were generated, ankylosis was found in some animals. This study revealed that implantation of a tooth germ‐like structure generated a complete tooth with a high success rate. The implant location may influence the morphology of the regenerated tooth.     

Transgenic expression of murine chemokine decoy receptor <Emphasis Type="Italic">D6</Emphasis> by islets reveals the role of inflammatory CC chemokines in the development of autoimmune diabetes in NOD mice

Aims/hypothesis  

Autoimmune diabetes results from a progressive destruction of insulin-producing beta cells in the pancreatic islets by chemokine-attracted lymphocytes. Because islet cells in NOD mice produce chemokines during the development of autoimmune diabetes, we investigated the role of inflammatory CC chemokines in disease progression in these mice.     

Cavum septum pellucidum: a feasible route to third ventricle

Tumors located within the third ventricle have some potential limitations during surgical approach. Generally speaking, it is impossible to reach the third ventricle without incision of any neural structure. We report a patient with choroid glioma in the anterior part of the third ventricle, and coincident cavum septum pellucidum (CSP) in whom we could remove the tumor gross totally without damaging any neurovascular structures. The tumor expanded the space between the rostrum of the corpus callosum and the column of the fornix and lifted up the floor of CSP. The transcavum-septum-pellucidum approach anterior to foramen of Monro was chosen to remove the anterior third ventricle tumor. We propose that the tumor had likely expanded within the above-mentioned space and elevated the floor of CSP thus increasing the anteroposterior diameter of the floor providing a feasible avenue to third ventricle making it feasible to pass through the enlarged space safely. Overall, cavum septum pellucidum provided a feasible route to approach the anterior third ventricle directly.     

Osteopontin regulates human glioma cell invasiveness and tumor growth in mice

Human malignant glioma cells are characterized by local invasion. In the present study, we investigated the role of osteopontin (OPN) in the invasiveness of human glioma cells isolated from grade IV tumors. We found that the expression levels of OPN in these cell lines paralleled matrix metalloproteinase-2 (MMP-2) expression and cell invasiveness potential. When U87MG glioma cells (with a high-OPN expression level) were stably transformed with specific small hairpin RNA to knock down OPN expression, MMP-2 secretion, cell invasiveness, and tumor growth in implanted brains were dramatically reduced. Conversely, forced expression of OPN in GBM-SKH glioma cells (which expressed OPN at a low level) increased MMP-2 secretion, enhanced cell invasiveness, and increased tumor growth in a rodent xenograft model. Expression of OPN was associated with increased expression of vimentin and decreased expression of glial fibrillary acidic protein. Treatment of glioma cells with 5-aza-2′-deoxycytidine (5-aza-dC) suppressed OPN expression in a concentration-dependent manner. Suppression of OPN expression by 5-aza-dC was associated with reductions in MMP-2 secretion, vimentin expression, cell invasion, intravasation, and tumor growth. These data suggest that OPN may play important roles in regulating cell invasion in glioma cells and that 5-aza-dC may serve as a therapeutic agent for human gliomas.