TEX-VAL: Texas A&M Tissue Chip Validation Consortium

项目摘要 德克萨斯A&M组织芯片验证联盟 该建议是为了促进德克萨斯A&M大学组织芯片验证中心的发展。 瓦尔）纳入TEX-瓦尔Consortium，以确认微生理系统（MPS）。TEX-VAL联盟的目标 是通过创造一个“安全港”，促进行业和监管机构使用组织芯片， 建立在TEX-VAL现有基础设施和专业知识基础上的私人伙伴关系，没有潜在的冲突 对组织芯片的发展很感兴趣在不到2年的时间里，2016年10月至2018年8月，TEX-VAL 完成了其他NIH资助者开发的11种组织芯片的测试。TEX-VAL已建立的功能， 组织芯片模型的可重复性、鲁棒性和可靠性可用于广泛的人体组织。其中包括 华盛顿大学近端肾小管;范德比尔特大学神经血管科;哥伦比亚大学 大学骨肿瘤和皮肤;约翰霍普金斯/贝勒医学院肠类;加州大学伯克利分校心脏，肝脏 和白色脂肪;加州大学欧文分校血管化肿瘤;杜克大学骨骼肌;匹兹堡大学 肝脏使用标准化工作流程对每个组织芯片进行测试，该工作流程包括材料转移（第1层）、测试 流动和药物与器械的结合（第0层），重复开发人员进行的实验 (Tier 1），以及与NIH、iQ Consortium和FDA合作选择的新药测试（Tier 2）。使 与标准体外系统的比较分析，所有的组织芯片实验都与 相关的二维文化质量保证项目计划由一名教员制定和审核， 在适用准则方面的经验。所有实验方案和记录都符合最高标准 根据经济合作与发展组织关于描述非指南的指南 体外方法，以及FDA和 国家毒理学计划。所有数据和协议都与各自的开发人员共享，并存入 匹兹堡大学微生理学系统数据库（MPS-Db）。在下一阶段的融资中， TEX-VAL联盟将利用德克萨斯A&M大学现有的基础设施进行表型分析和成像， 生物科学和技术研究所（Houston，TX）和兽医学院（学院站， 德克萨斯州），地球科学与环境研究小组（学院站，德克萨斯州）的分析化学，以及 纳米生物系统实验室（德克萨斯州学院站）的微流体学。TEX-VAL中心已经安全 承诺测试NIH资助的开发人员的19种新组织芯片。还有一些 iQ联盟和政府机构的主要成员承诺， NIH资助的组织芯片测试模型，以一个资助和管理的公私合作伙伴关系。最后， TEX-VAL与美国和欧洲的相关监管机构建立了广泛的合作关系网络， 这将继续作为与不同利益相关者进行沟通的重要渠道， 科学前景、技术稳健性以及所测试的组织芯片的任何限制。

PROJECT SUMMARY TEX-VAL: Texas A&M Tissue Chip Validation Consortium This proposal is to facilitate the evolution of the Tissue Chip Validation Center at Texas A&M University (TEX- VAL) into TEX-VAL Consortium for validation of microphysiological systems (MPS). TEX-VAL Consortium's goal is to promote the use of tissue chips by the industry and regulatory bodies by creating a “safe harbor” public- private partnership that builds on an existing infrastructure and expertise of TEX-VAL, free of potential conflicts of interests in tissue chip development. In less than 2 years, between October 2016 and August 2018, TEX-VAL completed testing of 11 tissue chips developed by other NIH grantees. TEX-VAL established functionality, reproducibility, robustness and reliability of tissue chip models for a wide array of human tissues. These included the University of Washington proximal kidney tubule; Vanderbilt University neuro-vascular unit; Columbia University bone-tumor and skin; Johns Hopkins/Baylor College of Medicine gut enteroid; UC-Berkeley heart, liver and white fat; UC-Irvine vascularized tumor; Duke University skeletal muscle; and the University of Pittsburgh liver. Each tissue chip was tested using a standardized workflow consisting of material transfer (Tier -1), testing of the flow and drug binding to the devices (Tier 0), replication of the experiments performed by the developers (Tier 1), and testing of new drugs selected in partnership with NIH, iQ Consortium, and FDA (Tier 2). To enable comparative analyses with standard in vitro systems, all tissue chip experiments were conducted in parallel with relevant 2D cultures. Quality assurance project plans were developed and audited by a faculty member with experience in applicable guidelines. All experimental protocols and records adhered to the highest standards based on the Organisation for Economic Cooperation and Development guidance for describing non-guideline in vitro methods, and appropriate guidance on validation of alternatives to animal methods from the FDA and the National Toxicology Program. All data and protocols were shared with respective developers and deposited into the University of Pittsburgh Microphysiology Systems Database (MPS-Db). In the next phase of funding, the TEX-VAL Consortium will utilize Texas A&M University's existing infrastructure for phenotyping and imaging at the Institute of Biosciences and Technology (Houston, TX) and College of Veterinary Medicine (College Station, TX), analytical chemistry at the Geosciences and Environmental Research Group (College Station, TX), and microfluidics at the NanoBio Systems Laboratory (College Station, TX). TEX-VAL Center already secured commitments for testing of 19 new tissue chips from NIH-funded developers. There are also a number of commitments from key members of the iQ Consortium and government agencies to negotiate transition from NIH-funded model for tissue chip testing to one funded and administered as a public-private partnership. Finally, TEX-VAL has an extensive network of partnerships with relevant regulatory agencies in the USA and Europe, which will continue to serve as an important channel for engagement with diverse stakeholders to communicate the scientific promise, technical robustness, as well as any limitations of the tested tissue chips.