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授权的主要目的是获得初步数据，以帮助我们评估细胞器械制造过程的一致性以及离体生产口腔粘膜等效物（EVPOME）细胞组分在制造过程中的活性一致性。目前，我们已成功获得CBER/FDA批准，启动了一项针对5名患者的概念验证临床试验，BB-IND #10118，“体外产生的口腔粘膜复合物的口内移植”。我们预计在2005年夏天招募第一个病人。这项研究将在密歇根大学NIH资助的一般临床研究中心（GCRC）进行。EVPOME将在人类应用实验室（HAL）生产，该实验室已获得良好生产规范（GMP）的批准，允许体外制备人体组织，用于移植回人体。已经启动了在密歇根大学进行I-II期临床试验的计划，以在我们成功完成涉及5名患者的原理研究证明后评估我们的非基因修饰或“幼稚”EVPOME移植物的口内移植的安全性。具体目标：开发非侵入性技术，以确定EVPOME生产过程中细胞组分的活力和代谢活性以及形态。假设：“离体产生的口腔粘膜等同物（EVPOME）或“幼稚”移植物”，在不含血清、转化的辐照饲养细胞和垂体提取物的规定组织培养基中开发，可进行非侵入性监测，而不会丧失细胞组分的活力或功能”。这将通过使用以下非侵入性技术来实现：1。葡萄糖利用测定以评估细胞活力和代谢活性，2.基于表面增强激光解吸/电离（SELDI）概念的Ciphergen Biosystems ProteinChip（r）系统，以评估与细胞活力和功能相关的口腔角质形成细胞的组成性产物如人b-防御素1的释放，3.反射共聚焦显微镜，以产生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，优化和验证一种技术和方法，以快速，非侵入性和定量地感测组织中的内源性荧光团。本研究的数据将允许继续开发“仿生量表”，以评估EVPOME是否适合放回其人体自体宿主，并在其制造过程中形成器械/产品质量保证的基础。