title: Development of a tissue-engineered human oral mucosa: from the bench to the bed side.
abstract: The main objective of this publication is to make the reader aware of the complexity and steps that are necessary to make a Food and Drug Administration (FDA)-approved laboratory produced cell-based device, for use in clinical trials for reconstructive surgery. Most tissue-engineered cell-based devices are considered as 'human somatic cell therapy' and fall under the auspices of the Center of Biologic Evaluation and Research (CBER) and are considered a combination product by the FDA. We have illustrated the algorithm that is necessary to follow an Independent New Drug (IND) application by using our ex vivo produced oral mucosa equivalents (EVPOME), a tissue-engineered oral mucosa, as an example of a cell-based device that needs FDA approval prior to clinical application. By illustrating the experimental approach and presenting resulting data we attempt to explain each step that we address along the way.
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of Michigan Medical Center, Ann Arbor, Mich., USA.
authors.forename: Kenji
authors.initials: K
authors.lastname: Izumi
authors.forename: Junhui
authors.initials: J
authors.lastname: Song
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Feinberg
mesh_terms: D000818:Animals; D002196:Capillaries / Q000166:cytology; D018929:Cell Culture Techniques / Q000379:methods; D002455:Cell Division / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D003094:Collagen / Q000627:therapeutic use; D018795:Device Approval / Q000331:legislation & jurisprudence; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology; D005947:Glucose / Q000378:metabolism; D006085:Graft Survival / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D017387:Investigational New Drug Application / Q000379:methods; D015603:Keratinocytes / Q000166:cytology / Q000637:transplantation / Q000648:ultrastructure; D019394:Ki-67 Antigen / Q000032:analysis; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D016513:Mice, SCID; D008854:Microscopy, Electron; D023421:Models, Animal; D009061:Mouth Mucosa / Q000166:cytology* / Q000637:transplantation; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D013518:Surgery, Plastic; D023822:Tissue Engineering / Q000379:methods*; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: C440568:Alloderm; C081876:CKAP4 protein, human; D019394:Ki-67 Antigen; D008565:Membrane Proteins; D018809:Proliferating Cell Nuclear Antigen; D003094:Collagen; D005947:Glucose