EAGER: Synergistic Influences of Oscillating Pressure and Growth Factor on Chondrogenesis in a Novel Centrifugal Bioreactor

EAGER：振荡压力和生长因子对新型离心生物反应器中软骨形成的协同影响

• 批准号: 1212573
• 负责人: Bernard Van Wie
• 金额: $ 18.2万
• 依托单位: Washington State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1212573&HistoricalAwards=false
• 关键词: EAGER; Synergistic; Influences; Oscillating; Pressure

1212573/ Van WieCartilage regenerative medicine for osteoarthritis will be advanced signifi-cantly by improved fundamental understanding at the cellular level of the complex interplay of mechanical and biochemical stimuli needed to create healthy cartilage. The central hypothesis posed by these investigators is that optimal differentiation of human mesenchymal stem cells (hMSCs) occurs via exposure to bioactive molecules combined with physical stimuli that promote membrane N-cadherin de-pendent cellular junctions. The researchers investigate our hypothesis using a unique continuous centrif-ugal bioreactor (CCBR) in this industry-university collaborative EAGER project. Intellectual Merit:The strength of this research program is the collaborative interface between biology, engineering and technology. WSU engineers will provide the novel bioreactor and AFM analytical technology, and REGN scientists will provide genetics and cell biology expertise. The research is : 1) to grow and differentiate hMSCs in the CCBR; 2) to determine the addi-tive and synergistic influences of multiple stimuli on chondrogenesis; and 3) to establish the relative contributions and synergistic impacts of various stimuli on mRNA upregulation and expression of proteins responsible for signaling pathways and mechano-transduction mechanisms responsible for heightened chondrogenic differentiation of hMSCs. The work could yield potential commercial application for autologous chondrocyte tissue culture systems for regenerative implants. Broader impact:Teaching & training: Presentations will be given on synergistic stimuli on chondrogenesis at REGN, and annual NIH Protein Biotechnology Training Program symposia; Representation: A U.S. woman and/or minority PhD student is being recruited to join the pro-gram through an anticipated NSF Graduate Research Supplement; Infrastructure: A new CCBR will be developed capable of imparting multiple stimuli for mechanotransduction studies; Dissemination at AIChE and ACS meetings and in technical journals; Societal Benefits: The work is expected to have long-term impact on regenerative cartilage repair and other tissue culture applications that impact human health.

1212573/货车WieCarbohydrate再生医学骨关节炎将是先进的显着提高基本理解在细胞水平的复杂相互作用的机械和生物化学刺激需要创造健康的软骨。这些研究人员提出的中心假设是，通过暴露于生物活性分子结合促进膜N-钙粘蛋白依赖性细胞连接的物理刺激，发生人间充质干细胞（hMSCs）的最佳分化。研究人员在这个工业-大学合作的EAGER项目中使用独特的连续离心生物反应器（CCBR）来研究我们的假设。智力优势：该研究计划的优势是生物学，工程和技术之间的协作界面。WSU工程师将提供新型生物反应器和AFM分析技术，REGN科学家将提供遗传学和细胞生物学专业知识。该研究是：1）在CCBR中生长和分化hMSC; 2）确定多种刺激对软骨形成的相加和协同影响;和3）建立各种刺激对负责信号传导途径和机械转导机制的蛋白质的mRNA上调和表达的相对贡献和协同影响，所述信号传导途径和机械转导机制负责hMSC的增强的软骨形成分化。 这项工作可能会产生潜在的商业应用自体软骨细胞组织培养系统再生植入物。更广泛的影响：教学&培训：将在REGN和年度NIH蛋白质生物技术培训计划专题讨论会上就软骨形成的协同刺激进行演讲;代表：正在招募一名美国女性和/或少数民族博士生通过预期的NSF研究生研究补充加入该计划;基础设施：将开发一种新的CCBR，能够为机械转导研究提供多种刺激;在AIChE和ACS会议和技术期刊上传播;社会效益：这项工作预计将对再生软骨修复和影响人类健康的其他组织培养应用产生长期影响。