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，以帮助我们评估细胞设备制造过程的均匀性以及离体生产的口腔粘膜细胞成分活力的一致性制造过程中的等效物 (EVPOME)。目前，我们已成功获得 CBER/FDA 批准，启动对 5 名患者进行概念验证的临床试验，BB-IND #10118，“Ex Vivo 生产的口腔粘膜复合材料的口内移植”。我们预计在 2005 年夏天招募第一位患者。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) 中生产，该实验室已获得良好生产规范 (GMP) 批准，允许离体制备人体组织，以便移植回人体。一旦我们成功完成了涉及 5 名患者的原理证明研究，计划已在密歇根大学启动一项 l-ll 期临床试验，以评估我们的非转基因或“原始”EVPOME 移植物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 在制造过程中的活力和代谢活性以及细胞成分的形态。假设：“离体产生的口腔粘膜等效物（EVPOME）或“原始”移植物”，在确定的组织培养基中开发，不含血清、转化的辐照饲养细胞和垂体提取物，可以无创、无损失地进行监测细胞成分的活力或功能”。这将通过使用以下非侵入性技术来完成：1. 葡萄糖利用测定，以评估细胞活力和代谢活性，2. Ciphergen Biosystems ProteinChip(r)系统基于表面增强激光解吸/电离 (SELDI) 的概念，用于评估口腔角质形成细胞的组成产物的释放，例如与细胞活力和功能相关的人 b-防御素 1，3. 反射共聚焦显微镜产生 EVPOME 在其天然状态下的实时高分辨率光学切片，以评估其在制造过程中的形态发展，以及 4. 荧光寿命光谱和成像，以开发、优化、并验证一种快速、非侵入性、定量检测组织中内源荧光团的技术和方法。这项调查的数据将允许继续开发“仿生量表”来评估 EVPOME、是否适合放回到人类自体宿主中，并为设备/产品在制造过程中的质量保证奠定基础。