Ex vivo development of a composite human oral mucosal equivalent

Izumi, Kenji; Takacs, Gyula; Terashi, Hiroto; Feinberg, Stephen E.

doi:10.1016/s0278-2391(99)90077-0

Cited by 91 publications

(83 citation statements)

References 27 publications

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“…Several investigations have reported on the use of either AlloDerm or deepidermized human dermis in the devel-opment of reconstituted skin and oral mucosa. [13][14][15][16][17] We reported on the characteristics of an ex vivo-produced oral mucosa equivalent (EVPOME) utilizing AlloDerm in a serum-free, defined medium, without an irradiated xenogeneic feeder layer. 18 In preparation for human clinical trials it was necessary to optimize the culture protocol for the in vivo grafting of EVPOME.…”

Section: Introduction Smentioning

confidence: 99%

Evaluation of Transplanted Tissue-Engineered Oral Mucosa Equivalents in Severe Combined Immunodeficient Mice

et al. 2003

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The aim of this study was to determine the optimal stage of development at which transplant human ex vivo-produced oral mucosa equivalents (EVPOMEs) in vivo. EVPOMEs were generated in a serum-free culture system, without the use of an irradiated xenogeneic feeder layer, by seeding human oral keratinocytes onto a human cadaveric dermal equivalent, AlloDerm. EVPOMEs were cultured for 4 days submerged and then for 7 or 14 days at an air-liquid interface to initiate stratification before transplantation into SCID mice. AlloDerm, without epithelium, was used as a control. Mice were killed on days 3, 10, and 21 posttransplantation. Epithelium of the transplanted EVPOMEs was evaluated with the differentiation marker keratin 10/13. Dermal microvessel ingrowth was determined by immunohistochemistry with a mouse vascular marker, lectin binding from Triticum vulgaris. The presence and stratification of the epithelium were correlated with revascularization of the underlying dermis. The microvessel density of AlloDerm without epithelium was less than that of EVPOMEs with an epithelial layer. Microvessel density of the dermis varied directly with the degree of epithelial stratification of the EVPOMEs. The EVPOMEs cultured at an air-liquid interface for 7 days had the optimal balance of neoangiogenesis and epithelial differentiation necessary for in vivo grafting. 163

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Section: Introduction Smentioning

confidence: 99%

Evaluation of Transplanted Tissue-Engineered Oral Mucosa Equivalents in Severe Combined Immunodeficient Mice

et al. 2003

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“…The detailed protocol for manufacturing EVPOMEs was described previously (Izumi et al 1999). Briefly, 200,000 oral keratinocytes/cm 2 were seeded on a 1-cm 2 acellular cadaver skin (AlloDerm™; LifeCell Corporation, Branchburg, NJ) that was presoaked in 0.05 µg/µL human type IV collagen (Sigma-Aldrich).…”

Section: Evpomes Manufacturing and Histologymentioning

confidence: 99%

“…An example of 3D tissue-engineered human oral mucosa is the ex vivo-produced oral mucosa equivalent (EVPOME) prepared using primary human oral keratinocytes (Izumi et al 1999). The quality of EVPOMEs before grafting into patients affects the success of graft take and tissue maturation of the EVPOMEs in vivo, so evaluation becomes an important issue to ensure the success of tissue-engineered construct implantation.…”

Section: Introductionmentioning

confidence: 99%

Biochemical Indicators of Implantation Success of Tissue-Engineered Oral Mucosa

et al. 2014

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Real-time (RT) determination of the health of in vitro tissue-engineered constructs prior to grafting is essential for prediction of success of the implanted tissue-engineered graft. In addition, the US Food and Drug Administration requires specific release criteria in RT prior to the release of tissue-engineered devices for human use. In principle, assessing the viability and functionality of the cellular component can be achieved by quantifying the secretion of growth factors and chemokines of tissue-engineered constructs. Ex vivo-produced oral mucosa equivalents (EVPOMEs) were fabricated under thermally stressed conditions at 43 °C for 24 h to create a functionally compromised EVPOME. We used microchannel enzyme-linked immunosorbent assay to evaluate the functionality of the cellular component, oral keratinocytes, of stressed and unstressed EVPOMEs by measuring the release of vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), human β-defensin 1 (hBD-1), and tissue inhibitor of metalloproteinase 1 and 2 (TIMP-1 and -2) into the spent medium, which was collected on the same day prior to graft implantation into severe combined immunodeficiency mice. Implanted EVPOMEs' histology on the seventh postimplantation day was used to correlate outcomes of grafting to secreted amounts of IL-8, hBD-1, VEGF, TIMP-1, and TIMP-2 from corresponding EVPOMEs. Our findings showed that significantly higher levels of IL-8, hBD-1, and TIMP-2 were secreted from controls than from thermally stressed EVPOMEs. We also found a direct correlation between secreted VEGF and IL-8 and blood vessel counts of implanted EVPOMEs. We concluded that measuring the constitutive release of these factors can be used as noninvasive predictors of healthy tissue-engineered EVPOMEs in RT, prior to their implantation.

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“…Tissue generated in this manner have been used for autologous tissue grafts for many years. 36 Oral tissues can be generated by harvesting cells from the oral cavity, expanding them, and growing them in a 3D tissue before engraftment. 37,38 Recently, 3D, skin-like tissues have been approved for clinical use in the treatment of periodontal disease.…”

Section: Tissue Engineering Of Complex Tissues Using Ipsc-derived Cellsmentioning

confidence: 99%

Strategies for Oral Mucosal Repair by Engineering 3D Tissues with Pluripotent Stem Cells

Hewitt

Shamis

Gerami‐Naini

et al. 2014

Advances in Wound Care

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Ex vivo development of a composite human oral mucosal equivalent

Cited by 91 publications

References 27 publications

Evaluation of Transplanted Tissue-Engineered Oral Mucosa Equivalents in Severe Combined Immunodeficient Mice

Evaluation of Transplanted Tissue-Engineered Oral Mucosa Equivalents in Severe Combined Immunodeficient Mice

Biochemical Indicators of Implantation Success of Tissue-Engineered Oral Mucosa

Strategies for Oral Mucosal Repair by Engineering 3D Tissues with Pluripotent Stem Cells

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