The expression and production of vascular endothelial growth factor in oral mucosa equivalents

Nakanishi, Yoshitaka; Izumi, Kenji; Yoshizawa, Michiko; Saito, Chikara; Kawano, Yoshiro; Maeda, Takeyasu

doi:10.1016/j.ijom.2007.06.013

Cited by 21 publications

(19 citation statements)

References 24 publications

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“…8 One would postulate that AlloDerm grafts without cells would take longer to heal, as there are no cellular components (oral keratinocytes) present that have the capability of secreting proangiogenic cytokines, such as vascular endothelial growth factor. 7,20 For smaller wounds this might not be critical, but with the larger defects seen in oral and maxillofacial reconstruction cases, the EVPOME would be more efficacious to use. More recently, Jhaveri et al reported favorable results with AlloDerm seeded with autologous gingival fibroblasts, as compared to conventional connective tissue grafting for the treatment of Miller Class I and II gingival recession.…”

Section: Discussionmentioning

confidence: 99%

Intraoral Grafting of Tissue-Engineered Human Oral Mucosa

Izumi

Neiva

Feinberg

2013

Int J Oral Maxillofac Implants

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Purpose The primary objective of this study was to evaluate the safety of a tissue-engineered human ex vivo–produced oral mucosa equivalent (EVPOME) in intraoral grafting procedures. The secondary objective was to assess the efficacy of the grafted EVPOME in producing a keratinized mucosal surface epithelium. Materials and Methods Five patients who met the inclusion criteria of having one mucogingival defect or a lack of keratinized gingiva on a nonmolar tooth, along with radiographic evidence of sufficient interdental bone height, were recruited as subjects to increase the width of keratinized gingiva at the defect site. A punch biopsy specimen of the hard palate was taken to acquire oral keratinocytes, which were expanded, seeded, and cultured on an acellular dermal matrix for fabrication of an EVPOME. EVPOME grafts were applied directly over an intact periosteal bed and secured in place. At baseline (biopsy specimen retrieval) and at 7, 14, 30, 90, and 180 days postsurgery, Plaque Index and Gingival Index were recorded for each subject. In addition, probing depths, keratinized gingival width, and keratinized gingival thickness were recorded at baseline, 30, 90, and 180 days. Results No complications or adverse reactions to EVPOME were observed in any subjects during the study. The mean gain in keratinized gingival width was 3 mm (range, 3 to 4 mm). The mean gain in keratinized gingival thickness was 1 mm (range, 1 to 2 mm). No significant changes in probing depths were observed. Conclusion Based on these findings, it can be concluded that EVPOME is safe for intraoral use and has the ability to augment keratinized tissue around teeth. Future clinical trials are needed to further explore this potential.

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Section: Discussionmentioning

confidence: 99%

Intraoral Grafting of Tissue-Engineered Human Oral Mucosa

Izumi

Neiva

Feinberg

2013

Int J Oral Maxillofac Implants

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“…Our previous study demonstrated the soluble VEGF molecules were intensely immunostained in basal and suprabasal layers in EVPOME. 15 Thus, VEGF was chosen as a cytokine biomarker, and its relationship between the metabolic activity of EVPOME by MTT assay and the release level quantitatively was measured over different days in culture.…”

Section: Discussionmentioning

confidence: 99%

“…This was consistent with the VEGF expression pattern in Day 11 EVPOME found at both mRNA and protein levels. 15 It is thus likely that the oral keratinocytes in basal and suprabasal layers within the EVPOME are the viable cells that also secret VEGF. Since mitosis has been present in the basal layer of normal epithelium giving rise to daughter cells that move upward and differentiate to form the keratinized layer,27 this suggested tissue renewal and differentiation seen within the EVPOME is similar to that in native oral mucosa.…”

Section: Discussionmentioning

confidence: 99%

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Constitutive Release of Cytokines by Human Oral Keratinocytes in an Organotypic Culture

Izumi

Tobita

et al. 2009

Journal of Oral and Maxillofacial Surgery

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The FDA requires an accurate determination of the dose and potency of tissue engineered or combinational products as is required for drugs. This needs to be done as a rapid, quantitative and non-invasive measurement of biological function/activity in a way as not to perturb the tissue engineered product being developed.Purpose-The aim of this study was to correlate constitutive release of cytokine(s) from unstimulated cells, at different stages of development within a three-dimensional (3D) organotypic ex vivo produced oral mucosa equivalent (EVPOME) to be used for intraoral grafting, with oral keratinocyte cell viability of the EVPOME.Materials and methods-Tissue culture media was assayed with an ELISA from monolayer culture of oral keratinocytes and a 3D EVPOME to determine the constitutive release of IL-1α, IL-6, IL-8 and VEGF. VEGF mRNA expression by oral keratinocytes within the 3D EVPOME were detected by in situ hybridization at day 4, 7 and 11. The number of viable oral keratinocytes within the EVPOME was extrapolated from VEGF release using a modified MTT assay. Conclusions-These results suggest that the increasing detectable levels of VEGF associated with the increasing number of viable cells in the EVPOME may provide a useful non-invasive/nondestructive means of assessing both cellular viability (dose) and biological function/activity (potency) of a combinational cell-based device such as the EVPOME. Results-Both

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“…An ex vivo synthesized oral mucosa equivalent (EVPOME) produced without using animal-derived serum or feeder layer cells [54, 85] has demonstrated its ability to promote early initiation of epithelialization, short healing period and minimal scar contraction. This can be partially explained by the ability of this living construct to secrete growth factors as VEGF, promoting initial vascularization, which is critical to subsequent graft survival [86, 87]. EVPOME has been successfully used to treat patients affected by squamous cell carcinoma of the tongue, leukoplakia of the tongue, gingiva, and buccal mucosa or hypoplasia of the alveolar ridge [54].…”

Section: Cell Therapy Applications For Craniofacial Regenerationmentioning

confidence: 99%