Characterization of Shearing Flow as an Osteoinductive *

剪切流作为骨诱导的表征*

• 批准号: 6868127
• 负责人: Aaron Sanford Goldstein
• 金额: $ 7.53万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6868127
• 关键词: biological transport; biotechnology; bone development; bone marrow; cell adhesion; cell differentiation; cell growth regulation; cell type; fibronectins; intermolecular interaction; laboratory rat; osteoblasts; polymerase chain reaction; statistics /biometry; stem cell factor; stem cell transplantation; stem cells; tissue /cell culture; tissue engineering; tissue support frame

Bone marrow stromal stem cells (BMSCs) are multipotent progenitor cells that have great potential as an osteoinductive and osteogenic component for engineered bone tissue. Incorporation of these cells into clinically effective graft materials relies on the establishment of in vitro culture techniques that can direct expansion and preferential differentiation into the osteoblastic lineage. Successful techniques would lead to the creation of a bone-like tissue replete with osteoconductive and osteoinductive factors to stimulate host integration and remodeling. Building on our evidence that BMSCs are mechanosensitive and that flow stimulates phenotypic markers of osteoblastic maturation, we seek to understand how flow modulates phenotypic markers. The specific aims of this project involve systematic evaluation of three complementary components of a perfusion strategy. 1) Characterize the effect of shear stress magnitude and mass transport rate on expression of phenotypic markers of osteoblastic differentiation. 2) Assess the impact of intermittent flow strategies on osteoblastic differentiation. 3) Characterize the effect of adhesive ligand activity on differentiation and probe for synergy with shearing flow. The proposed studies - involving osteoprogenitor cells suitable for bone tissue engineering applications -will be performed under well-characterized conditions in a parallel-plate flow chamber to identify osteoinductive transport effects of perfusion, establish benchmarks of osteoblastic differentiation, and determine effective culture strategies. These findings will be used to predict optimal culture conditions for osteoblastic differentiation of BMSCs within perfused 3D scaffold geometries, with the goal of producing engineered bone tissues suitable for clinical testing.

骨髓基质干细胞(BMSCs)是一种多能的前体细胞，在工程化骨组织中具有巨大的骨诱导和成骨成分的潜能。将这些细胞整合到临床有效的移植材料中依赖于体外培养技术的建立，该技术可以指导扩增和优先分化为成骨细胞系。成功的技术将导致产生一种充满骨传导和骨诱导因子的类骨组织，以刺激宿主整合和重塑。基于我们的证据，骨髓间充质干细胞是机械敏感的， 为了刺激成骨细胞成熟的表型标记物，我们试图了解流动是如何调节表型标记物的。该项目的具体目标包括对灌流策略的三个互补部分进行系统评估。 1)研究切应力大小和传质速率对成骨细胞分化表型标志物表达的影响。 2)评估间歇性血流策略对成骨细胞分化的影响。 3)表征黏附配基活性对分化的影响，探讨与剪切流的协同作用。 拟议的研究--涉及适合骨组织工程应用的骨祖细胞--将在平行板流室中进行，以确定灌流的骨诱导运输效应，建立成骨细胞分化的基准，并确定有效的培养策略。这些发现将被用来预测BMSCs在灌流的3D支架几何结构中向成骨细胞分化的最佳培养条件，目标是生产适合临床测试的工程化骨组织。