Collagen turnover induced by cellular connective tissue cytokines of drug induced gingival overgrowth and hereditary gingival fibromatosis (Histological and immunohistochemical comparative study)

Background: Gingival overgrowth (GO) is usually associated with multiple factors including immunosuppressive agents as cyclosporine (CsA) and Tacrolimus (TAC), and hereditary gingival fibromatosis (HGF). Objective: To compare the expression of TGF-b1, PDGF, TIMP-1 and MMP-9 at the molecular and cellular levels in patients receiving (CsA or TAC) and patients manifested (HGF), to cast some light on the pathogenic mechanism potentially involved in the collagen (COL) turnover of both conditions. Subjects: and methods: Gingival tissue samples were obtained from patients undergoing therapy with CsA (n ¼ 6), TAC (n ¼ 6), HGF (n ¼ 3) as well as control tissues from systemically healthy control (n ¼ 6). Tissue sections were immune-stained by labeled streptavidin-biotin (DAB) technique, using monoclonal antibodies against TGF-b1, PDGF-b, TIMP-1 and MMP-9. Results: comparison of type of expression among the studied groups, showed significant diffuse expression of TGF-b1 and PDGF-b in group I and II with P value ¼ 0.58 and 0.38 respectively. The expression of MMP-9 was significantly diffuse in TAC or CsA group when compared to HGF group with P value ¼ 0.38, mean while there was a significant diffuse expression of TIMP-1 in HGF group when compared to TAC or CsA group with P value ¼ 0.38. Conclusions: In conclusion the biological mechanisms behind the drug induced gingival overgrowth (DIGO) and HGF is targeting COL turnover but in different ways. Also, this may explain the need for periodic surgical correction of the gingival form and architecture in HGF cases, unlike the DIGO which can be overcame by replacement of CsA by TAC with improvement of oral healt

Collagen turnover induced by cellular connective tissue cytokines of drug induced gingival overgrowth and hereditary gingival fibromatosis (Histological and immunohistochemical comparative study)

Background: Gingival overgrowth (GO) is usually associated with multiple factors including immuno- suppressive agents as cyclosporine (CsA) and Tacrolimus (TAC), and hereditary gingival fibromatosis (HGF).Objective: To compare the expression of TGF-b1, PDGF, TIMP-1 and MMP-9 at the molecular andcellularlevels in patients receiving (CsA or TAC) and patients manifested (HGF), to cast some light on the pathogenic mechanism potentially involved in the collagen (COL) turnover of both conditions. Subjects: and methods: Gingival tissue samples were obtained from patients undergoing therapy with CsA (n ¼ 6), TAC (n ¼ 6), HGF (n ¼ 3) as well as control tissues from systemically healthy control (n ¼ 6).Tissue sections were immune-stained by labeled streptavidin-biotin (DAB) technique, using monoclonal antibodies against TGF-b1, PDGF-b, TIMP-1 and MMP-9

Efficacy of Equine Demineralized Bone Matrix in treating Oral Cyst following Enucleation: A Histologic and Clinical study in Humans

Objectives:The aim of this study is to report the effect of equine demineralized bone matrix (DBM) on the healing of oral cystic cavities following enucleation using clinical parameters. Study design:Twelve patients aged from 20 to 40 years and suffering from cystic lesion in the jaw were included in this study. Cystic cavity augmentation with DBM was performed on 6 patients. After an average of 6 months’ healing period, a core bone was obtained and stained for histologic analysis simultaneously with implant placement. Results:Uneventful healing and spontaneous filling of the residual cavities was obtained in all cases. All implants showed favorable Osseointegration, and final restorations were completed without failure in all cases. Histologically, new bone formation was active around grafted bone, and grafted bone was well integrated to the newly formed bone matrix. In histomorphometric analysis, vital bone volume was 25.2 ±11.9%. Conclusion:The equine DBM is clinically useful for the increase of bone volume in cystic cavities after enucleation, because of its favorable effect of new bone formation and it is considered to be a safe, simple, reliable, acceptable, and easy handling bone grafting material

Efficiency of systemic versus intralesional bone marrow- derived stem cells in regeneration of oral mucosa after induction of formocresol induced ulcers in dogs

Background: Bone marrow mesenchymal stem cells (BMSCs) are the key to regenerative wound healing. MSCs have spatial memory and respond to local environment. The goal of this study was to evaluate the use of systemic and intralesional transplantation of BMSCs for regeneration of oral mucosa in an in vivo dog model. Materials and Methods: Transplantation of undifferentiated green fluorescent protein (GFP)-labeled autologous BMSCs systemically, submucosally or vehicle (saline) was injected around the chemically induced oral ulcer in each group of 18 adult dogs. The healing process of the ulcer was monitored clinically and histopathologically. Gene expression of vascular endothelial growth factor (VEGF) and collagen genes was detected in biopsies from all ulcers. One way ANOVA was used to compare between means of the three groups. Results were considered significant at P < 0.05. Results: Flow cytometric analysis of the MSCs at the passage 3 showed that these cells were negative for CD45 (2.39%). They expressed high levels of CD29 (98.34%). Frozen fluorescence microscopy of sections of the cell-treated oral tissue of all groups indicated that the GFP-transduced implanted cells were integrated within the transplanted tissues. The treatment resulted in dramatic wound edge activation and resurfacing of oral mucosa wound. Conclusion: Our results revealed that BMSCs may be labeled with (GFP), in order to know the distribution of these cells after administration, and suggest that intralesional administration is an appropriate procedure to achieve acceptable regeneration of the previously injured oral mucosa more than systemic route

Adipose Stem Cells as Alternatives for Bone Marrow Mesenchymal Stem Cells in Oral Ulcer Healing

BACKGROUND AND OBJECTIVES: Adipose tissue is now recognized as an accessible, abundant, and reliable site for the isolation of adult stem cells suitable for tissue engineering and regenerative medicine applications. METHODS AND RESULTS: Oral ulcers were induced by topical application of formocresol in the oral cavity of dogs. Transplantation of undifferentiated GFP-labeled Autologous Bone Marrow Stem Cell (BMSCs), Adipose Derived Stem Cell (ADSCs) or vehicle (saline) was injected around the ulcer in each group. The healing process of the ulcer was monitored clinically and histopathologically. Gene expression of vascular endothelial growth factor (VEGF) was detected in MSCs by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Expression of VEGF and collagen genes was detected in biopsies from all ulcers. RESULTS: MSCs expressed mRNA for VEGF MSCs transplantation significantly accelerated oral ulcer healing compared with controls. There was increased expression of both collagen and VEGF genes in MSCs-treated ulcers compared to controls. CONCLUSIONS: MSCs transplantation may help to accelerate oral ulcer healing, possibly through the induction of angiogenesis by VEGF together with increased intracellular matrix formation as detected by increased collagen gene expression. This body of work has provided evidence supporting clinical applications of adipose-derived cells in safety and efficacy trials as an alternative for bone marrow mesenchymal stem cells in oral ulcer healing

Adipose Stem Cells as Alternatives for Bone Marrow Mesenchymal Stem Cells in Oral Ulcer Healing

BACKGROUND AND OBJECTIVES: Adipose tissue is now recognized as an accessible, abundant, and reliable site for the isolation of adult stem cells suitable for tissue engineering and regenerative medicine applications. METHODS AND RESULTS: Oral ulcers were induced by topical application of formocresol in the oral cavity of dogs. Transplantation of undifferentiated GFP-labeled Autologous Bone Marrow Stem Cell (BMSCs), Adipose Derived Stem Cell (ADSCs) or vehicle (saline) was injected around the ulcer in each group. The healing process of the ulcer was monitored clinically and histopathologically. Gene expression of vascular endothelial growth factor (VEGF) was detected in MSCs by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Expression of VEGF and collagen genes was detected in biopsies from all ulcers. RESULTS: MSCs expressed mRNA for VEGF MSCs transplantation significantly accelerated oral ulcer healing compared with controls. There was increased expression of both collagen and VEGF genes in MSCs-treated ulcers compared to controls. CONCLUSIONS: MSCs transplantation may help to accelerate oral ulcer healing, possibly through the induction of angiogenesis by VEGF together with increased intracellular matrix formation as detected by increased collagen gene expression. This body of work has provided evidence supporting clinical applications of adipose-derived cells in safety and efficacy trials as an alternative for bone marrow mesenchymal stem cells in oral ulcer healing

Influence of Autologus Adipose Derived Stem Cells and PRP on Regeneration of Dehiscence-Type Defects in Alveolar Bone: A Comparative Histochemical and Histomorphometric Study in Dogs

Background and Objectives: Autogenous bone grafts is considered to be the best choice for reconstructive surgery. Adipose Derived Stromal Cells (ASCs) represents a promising tool for new clinical concepts in supporting cellular therapy. The goal of our study was to investigate bone regeneration following application of autologous ASCs with or without Platelet-Rich Plasma (PRP) at dehiscence-type defects in alveolar bone in dogs. Methods and Results: Standardized buccal dehiscence defects (4×3×3 mm) were surgically created in eighteen dogs, the defects were grafted with either ASCs -PRP, ASCs alone, or without grafting material. Three months later; a bone core was harvested from grafted and non grafted sites for histological, histochemical and histomorphometric assessment. There was no evidence of inflammation or adverse tissue reaction with either treatment. Defects grafted with ASCs-PRP showed a significantly higher result (p≤0.05), with a mean area % of spongy bone and compact bone of (64.96±5.37 and 837.62±24.95), compared to ASCs alone (47.65±1.43 and 661.92±12.65) and without grafting (33.55±1.74 and 290.85±7.27) respectively. The area % of lamellated bone increased significantly reaching its highest level in group A followed by group B. Also a significant increase in area % of neutral mucopolysaccharides and calcified reactivity of Masson's Trichrome stain in groups A and B compared to group C was obtained. Conclusions: Our results suggest that, the addition of PRP to ASCs enhances bone formation after 3 months and may be clinically effective in accelerating postsurgical healing in both periodontal and maxillofacial surgical applications

Influence of Autologus Adipose Derived Stem Cells and PRP on Regeneration of Dehiscence-Type Defects in Alveolar Bone: A Comparative Histochemical and Histomorphometric Study in Dogs

Background and Objectives: Autogenous bone grafts is considered to be the best choice for reconstructive surgery. Adipose Derived Stromal Cells (ASCs) represents a promising tool for new clinical concepts in supporting cellular therapy. The goal of our study was to investigate bone regeneration following application of autologous ASCs with or without Platelet-Rich Plasma (PRP) at dehiscence-type defects in alveolar bone in dogs. Methods and Results: Standardized buccal dehiscence defects (4×3×3 mm) were surgically created in eighteen dogs, the defects were grafted with either ASCs -PRP, ASCs alone, or without grafting material. Three months later; a bone core was harvested from grafted and non grafted sites for histological, histochemical and histomorphometric assessment. There was no evidence of inflammation or adverse tissue reaction with either treatment. Defects grafted with ASCs-PRP showed a significantly higher result (p≤0.05), with a mean area % of spongy bone and compact bone of (64.96±5.37 and 837.62±24.95), compared to ASCs alone (47.65±1.43 and 661.92±12.65) and without grafting (33.55±1.74 and 290.85±7.27) respectively. The area % of lamellated bone increased significantly reaching its highest level in group A followed by group B. Also a significant increase in area % of neutral mucopolysaccharides and calcified reactivity of Masson's Trichrome stain in groups A and B compared to group C was obtained. Conclusions: Our results suggest that, the addition of PRP to ASCs enhances bone formation after 3 months and may be clinically effective in accelerating postsurgical healing in both periodontal and maxillofacial surgical applications