We examined the effects of six xanthones from the pericarps of mangosteen, Garcinia mangostana, on the cell growth inhibition of human leukemia cell line HL60. All xanthones displayed growth inhibitory effects. Among them, alpha-mangostin showed complete inhibition at 10 microM through the induction of apoptosis.
The feasibility of an in situ tissue-engineering method employing cell-based therapy with autologous periodontal ligament-derived cells was investigated. Periodontal ligament cells were obtained from six beagle dogs. Periodontal fenestration defects (6 x 4 mm) were created bilaterally at a location 6 mm apical to the marginal alveolar crest in the maxillary canines. Alkaline phosphatase-positive periodontal ligament cells (3 x 10(5) cells) were seeded onto a collagen sponge scaffold just before implantation. One defect was filled with the cell-scaffold construct, and another was left empty as the control. All animals were killed 4 weeks after surgery, and specimens were evaluated histomorphometrically. All the histomorphometrical data were analyzed by three-way analysis of variance with the Bonferroni multiple comparisons test. Regeneration of apical tissue was faster than that of coronal and isolated tissues on the control side (apical > coronal > isolated; p < 0.0001). On the other hand, on the cell-seeded side, regeneration of the cementum was observed uniformly on the root surface. Our data suggest that the seeded cells induced cementum regeneration on the root surface, indicating the potential of in situ tissue engineering using autologous cells for the regeneration of periodontal tissues.
We examined the in vitro effects of the benzophenone derivatives garcinol, isogarcinol, and xanthochymol on cell growth in four human leukemia cell lines. All of the compounds exhibited significant growth suppression due to apoptosis mediated by the activation of caspase-3. A loss of mitochondrial membrane potential was found in garcinol-and isogarcinol-induced apoptosis, but not in xanthochymol-induced apoptosis. The growth inhibitory effects of isogarcinol and xanthochymol were more potent than that of garcinol, which is a well-known cytotoxic benzophenone derivative.
To regenerate periodontal tissues, a sandwich membrane composed of a collagen sponge scaffold and gelatin microspheres containing basic fibroblast growth factor (bFGF) in a controlled-release system was developed according to the new concept of "in situ tissue engineering." A three-walled alveolar bone defect (3 x 4 x 4 mm) was made bilaterally in edentulous regions created mesially to the canines in both the maxilla and mandible of nine beagle dogs. A sandwich membrane with or without bFGF (100 microg) was implanted in each defect (each group, n = 18). During weeks 1, 2, and 4, histologic evaluation and histometric analyses were performed on three dogs. Throughout the 4 weeks, vascularization and osteogenesis were active only in the bFGF-treated group (p < 0.01). New cementum was formed (2.4 +/- 0.9 mm) on the exposed root surface at 4 weeks, and functional recovery of the periodontal ligament was indicated in part by the perpendicular orientation of regenerated collagen fibers. In the control group, epithelial downgrowth and root resorption occurred and the defects were filled with connective tissue. Thus, our sandwich membrane induced successful regeneration of the periodontal tissues in a short period of time.
These results demonstrate that both rhBMP2 and rhBMP9 have osteopromotive properties on osteoblast differentiation. It was found that rhBMP9 additionally stimulated the osteopromotive potential of osteoblasts when compared to rhBMP2 by demonstrating higher levels of ALP expression and alizarin red staining. Further animal studies comparing both recombinant proteins are necessary to further characterize the osteoinductive potential of BMP9.
Results indicate that the combination of collagen membranes with rhBMP9 induced significantly higher ALP mRNA expression and alizarin red staining compared with rhBMP2. These findings suggest that rhBMP9 may be a suitable growth factor for future regenerative procedures in bone biology.
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