Mfg/Transport Ex Vivo Prod. Oral Mucosa Equivalents

制造/运输 Ex Vivo 产品。

• 批准号: 6916740
• 负责人: STEPHEN Elliott FEINBERG
• 金额: $ 15.3万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6916740
• 关键词: bioengineering /biomedical engineering; biomaterial compatibility; biomaterial development /preparation; biomaterial evaluation; biomaterial interface interaction; biotechnology; cell morphology; cell transplantation; clinical research; confocal scanning microscopy; flow cytometry; fluorescence spectrometry; fluorescent dye /probe; glucose metabolism; human subject; ionophores; medical implant science; molecular /cellular imaging; oral mucosa; surface enhanced laser desorption ionization; technology /technique development; tissue /cell preparation

DESCRIPTION (provided by applicant): The primary objective of our Clinical Pilot Data Grant is to obtain preliminary data to assist us in assessing uniformity of the manufacturing process of the cellular device and consistency in viability of the cellular component of the Ex Vivo Produced Oral Mucosa Equivalent (EVPOME) during its fabrication. At present, we have successfully received CBER/FDA approval to initiate a clinical trial for a proof of concept of 5 patients, BB-IND #10118, "Intraoral Grafting of Ex Vivo Produced Oral Mucosa Composites". We anticipate recruiting our first patient the summer of 2005. This study will be done in the University of Michigan's NIH-funded General Clinical Research Center (GCRC). The EVPOME will be produced in the Human Applications Laboratory (HAL), approved for Good Manufacturing Practice (GMP) that allows preparation of human tissue, ex vivo, for grafting back into humans. Plans have been initiated for a phase l-ll clinical trial at the University of Michigan to assess the safety of intraoral grafting of our non-genetically-modified or "naive" EVPOME grafts once we successfully completed the proof of principle study involving the 5 patients. Specific Aim: Development of non-invasive techniques, to determine viability and metabolic activity, and morphology of the cellular component of the EVPOME during its manufacturing process. Hypothesis: "Ex vivo produced oral mucosa equivalent (EVPOME), or "naive" grafts", developed in a defined tissue culture medium, free of serum, transformed irradiated feeder cells, and pituitary extract can be monitored, non-invasively, without loss of viability or function to the cellular component". This will be accomplished by using the following non-invasive techniques: 1. Glucose utilization assay to assess cellular viability and metabolic activity, 2. Ciphergen Biosystems ProteinChip(r)System based on the concept of surface-enhanced laser desorption/ionization (SELDI) to assess release of constitutive products of oral keratinocytes such as human b-defensin 1 that correlate with cell viability and function, 3. Reflectance confocal microscopy to yield real-time high resolution optical sections of EVPOME in its native state to assess its morphologic development through the manufacturing process, and 4. Fluorescence lifetime spectroscopy and imaging to develop, optimize, and validate a technology and method to rapidly, non-invasively, and quantitatively sense endogenous fluorophores in tissues. Data from this investigation will allow continued development of a "biomimetic scale" to assess EVPOME, suitability to be placed back into its human autogenous host as well as form a basis for quality assurance of the device/product during its fabrication process.

描述(由申请人提供)：我们的临床试验数据资助的主要目标是获得初步数据，以帮助我们评估蜂窝设备制造过程的一致性，以及Ex Vivo生产的口腔黏膜等效物(EVPOME)在制造过程中细胞成分的活性一致性。目前，我们已经成功地获得了CBER/FDA的批准，为5名患者启动了一项临床试验，以验证其概念，BB-IND#10118，“Ex Vivo生产的口腔黏膜复合材料的口腔内移植”。我们预计在2005年夏天招募我们的第一名患者。这项研究将在密歇根大学NIH资助的普通临床研究中心(GCRC)进行。EVPOME将在人类应用实验室(HAL)生产，该实验室获得了良好制造规范(GMP)的批准，允许体外准备人体组织，以便移植回人类体内。密歇根大学的L-11期临床试验计划已经启动，一旦我们成功完成涉及5名患者的原则研究，评估我们的非转基因或“幼稚”EVPOME移植物的口腔内移植的安全性。具体目标：开发非侵入性技术，以确定EVPOME在制造过程中的活性和代谢活性，以及细胞成分的形态。假设：“体外生产的口腔黏膜等效物(EVPOME)，或”幼稚的“移植物”，在特定的组织培养介质中发展，没有血清，转化的辐射饲养细胞，和脑垂体提取物可以非侵入性地监测，而不会损失细胞成分的活性或功能。这将通过使用以下非侵入性技术来完成：1.葡萄糖利用试验以评估细胞的活性和代谢活性，2.基于表面增强激光解吸/电离(SELDI)概念的Ciphergen BiosSystems ProteinChip(R)系统，以评估口腔角质形成细胞的构成产物的释放，例如与细胞活性和功能相关的人b-防御素1，3.反射共聚焦显微镜，以在其自然状态下产生实时高分辨率光学切片，以通过制造过程评估其形态发育，以及4.荧光寿命光谱和成像以开发、优化和验证快速、非侵入性、和验证的技术和方法并定量检测组织中的内源性荧光团。这项研究的数据将使“仿生量表”继续发展，以评估EVPOME的适宜性，将其放回其人类自体宿主，并形成设备/产品在制造过程中的质量保证的基础。