The role of hyaluronic acid, CD44 and osteopontin in haemopoietic stem cell biology

透明质酸、CD44和骨桥蛋白在造血干细胞生物学中的作用

• 批准号: nhmrc : 350446
• 负责人: Prof Susan Nilsson
• 金额: $ 31.48万
• 依托单位: Australian Stem Cell Centre Ltd
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2005
• 资助国家: 澳大利亚
• 起止时间: 2005-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/role-hyaluronic-acid-cell-biology/100353
• 关键词: role; hyaluronic; acid; CD44; osteopontin

Marrow and microenvironmental cell (MC) interactions play a central role in bone marrow (BM) cell localisation and regulation. Specifically, the regulation of primitive blood cells (HSC) is affected by their locality and their expression of a wide repertoire of cell adhesion molecules. This project is based upon the unique observations made in the applicants laboratory demonstrating that the three molecules hyaluronic acid (HA), CD44 and osteopontin play key roles in the localisation of HSC within the BM following transplantation and in regulating their development into mature blood cells. Encapsulating the concept of highly specific, local interactions regulating blood cells is the 'niche' hypothesis in which MC form a specific 'niche'. The current inability to identify HSC in situ makes it impossible to analyse either their distribution or molecules that regulate this process. Circumstantial evidence suggests the presence of HSC 'niches' in close association with the bone. Using a novel approach based on BM transplantation to track cells lodging in the BM, we were the first to report that the lodgement of a transplanted HSC is not a random process, but results in cells of donor origin migrating to the bone-marrow interface. The presence of HA and CD44 on the HSC and CD44 and ostepontin in the marrow microenvironment are critical for this pattern of lodgement. In addition, we now have evidence that HA and osteopontin are important in the maintenance of HSC in their primitive state. This proposal aims to confirm the critical roles and interactions of these three molecules in HSC biology.

骨髓和微环境细胞（MC）的相互作用在骨髓（BM）细胞定位和调节中起着核心作用。具体而言，原始血细胞（HSC）的调节受到其位置和广泛的细胞粘附分子库的表达的影响。该项目基于在申请人实验室中进行的独特观察，证明三种分子透明质酸（HA）、CD44和骨桥蛋白在移植后骨髓内HSC的定位和调节其发育成成熟血细胞中起关键作用。封装的概念，高度特异性，局部相互作用调节血细胞是“生态位”的假设，其中MC形成一个特定的“生态位”。目前无法在原位识别HSC，因此无法分析它们的分布或调节这一过程的分子。间接证据表明，HSC的“壁龛”的存在与骨密切相关。使用一种基于BM移植的新方法来跟踪BM中的细胞沉积，我们首次报道了移植的HSC的沉积不是一个随机过程，而是导致供体来源的细胞迁移到骨髓界面。HSC上的HA和CD 44以及骨髓微环境中的CD 44和骨桥蛋白的存在对于这种沉积模式至关重要。此外，我们现在有证据表明HA和骨桥蛋白在维持HSC的原始状态中是重要的。该提案旨在确认这三种分子在HSC生物学中的关键作用和相互作用。