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

通过提高对细胞水平上产生健康软骨所需的机械和生化刺激的复杂相互作用的基本理解，骨关节炎的软骨再生医学将得到显著进展。这些研究人员提出的中心假设是，人间充质干细胞（hMSCs）的最佳分化是通过暴露于生物活性分子和促进膜n -钙粘蛋白依赖的细胞连接的物理刺激发生的。在这个产学研合作的EAGER项目中，研究人员使用一种独特的连续离心生物反应器（CCBR）来验证我们的假设。智力优势：这个研究项目的优势在于生物、工程和技术之间的协作界面。华盛顿州立大学的工程师将提供新的生物反应器和AFM分析技术，REGN的科学家将提供遗传学和细胞生物学专业知识。研究方向为：1)在CCBR中培养和分化hMSCs；2)确定多种刺激对软骨形成的附加和协同影响；3)确定各种刺激对hMSCs软骨分化增强的信号通路和机械转导机制的mRNA上调和蛋白表达的相对贡献和协同影响。这项工作可能为再生植入物的自体软骨细胞组织培养系统带来潜在的商业应用。更广泛的影响：教学和培训：将在REGN进行关于软骨形成的协同刺激的演讲，以及年度NIH蛋白质生物技术培训计划专题讨论会；代表：一名美国女性和/或少数族裔博士生正通过预期的NSF研究生研究补充计划被招募加入该计划；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会议上以及在技术期刊上进行传播；社会效益：这项工作有望对再生软骨修复和其他影响人类健康的组织培养应用产生长期影响。

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.