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

1212573/Van WieCartilage骨关节炎再生医学将通过在细胞水平上更好地了解创建健康软骨所需的机械和生化刺激的复杂相互作用而显著进步。这些研究人员提出的中心假设是，人间充质干细胞(HMSCs)的最佳分化是通过接触生物活性分子和促进膜N-钙粘素依赖的细胞连接的物理刺激来实现的。在这个产学研合作项目中，研究人员使用了一种独特的连续离心式生物反应器(CCBR)来验证我们的假设。智力价值：这个研究项目的优势是生物学、工程学和技术之间的协作接口。威斯康星州立大学的工程师将提供新型生物反应器和原子力显微镜分析技术，REGN科学家将提供遗传学和细胞生物学专业知识。1)在CCBR中培养和分化hMSCs；2)确定多种刺激对软骨形成的相加和协同影响；以及3)确定不同刺激对hMSCs软骨分化的信号通路和机械转导机制相关蛋白的上调和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和年度NIH蛋白质生物技术培训计划专题讨论会上就协同刺激软骨形成发表演讲；陈述：通过预期的NSF研究生研究补充材料，正在招募一名美国妇女和/或少数族裔博士生加入该计划；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会议以及技术期刊上传播；社会益处：该工作预计将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.