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Role of CD44 in hematopoietic stem cell homing

CD44在造血干细胞归巢中的作用

基本信息

批准号：
6867287
负责人：
SOPHIA K KHALDOYANIDI
金额：
$ 19.55万
依托单位：
LA JOLLA INST FOR MOLECULAR MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-04-01 至 2007-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6867287
关键词：
CD44 molecule biological models cell cell interaction cell migration hematopoietic stem cells hematopoietic tissue transplantation human tissue method development model design /development protein structure function stem cell transplantation

项目摘要

DESCRIPTION (provided by applicant): Transplantation of hematopoietic stem cells (HSC) is a required procedure for patients who have undergone high-dose chemotherapy and irradiation, and its efficiency depends on the homing ability of HSC, e.g., capacity of the cells to enter the recipient's bone marrow and establish steady hematopoiesis. HSC homing is a complex process that includes multiple steps and is strictly regulated by adhesion molecules as well as soluble factors and the extracellular matrix. We have previously demonstrated that the CD44 adhesion molecule is one of the bone marrow homing receptors. However, the cellular and molecular mechanisms of CD44-mediated human HSC homing are still poorly understood. While existing techniques for studying HSC homing provide a large amount of important information, they do not allow us to distinguish between extravasated cells and cells arrested on the vascular endothelium, nor do they allow us to assess the influence of the hematopoietic microenvironment on endothelial cell function under conditions of physiological flow. Therefore, new in vitro methods are required to investigate the effects of the hematopoietic microenvironment on both HSC - endothelial cell and HSC - stromal cell interactions under shear stress conditions. As the first specific aim, we propose to utilize a new technique that would allow us to monitor the effect of the hematopoietic microenvironment on trafficking of human HSC, including rolling on, adhesion to, and transmigration across the endothelial layer, and the seeding of the bone marrow hematopoietic-supportive stroma under these conditions of physiological flow by utilizing a two-cell parallel flow chamber in vitro. In combination with a blot-rolling assay, this technique will help us to identify novel ligands and counter-receptors for CD44 and delineate the cellular and molecular mechanisms of CD44 - mediated homing of human HSC in vitro. The proposed studies will therefore define a new approach for studying homing of human HSC that can potentially provide a basis for the development of new strategies for stem cell transplantation following chemotherapy or total body irradiation.

描述（由申请人提供）：造血干细胞（HSC）移植是接受高剂量化疗和放疗的患者的必需程序，其效率取决于HSC的归巢能力，例如，细胞进入接受者骨髓并建立稳定造血的能力。HSC归巢是一个复杂的过程，包括多个步骤，并受到粘附分子以及可溶性因子和细胞外基质的严格调节。我们以前已经证明，CD44粘附分子是骨髓归巢受体之一。然而，CD44介导的人HSC归巢的细胞和分子机制仍然知之甚少。虽然现有的研究HSC归巢的技术提供了大量的重要信息，但它们不允许我们区分外渗细胞和在血管内皮上停滞的细胞，也不允许我们评估在生理流动条件下造血微环境对内皮细胞功能的影响。因此，需要新的体外方法来研究剪切应力条件下造血微环境对HSC-内皮细胞和HSC-基质细胞相互作用的影响。作为第一个具体目标，我们建议利用一种新的技术，使我们能够监测造血微环境对人HSC运输的影响，包括滚动，粘附和穿越内皮层，以及在这些生理流动条件下通过利用体外双细胞平行流动室接种骨髓造血支持基质。结合印迹滚动试验，该技术将帮助我们鉴定新的CD44配体和反受体，并描绘体外CD44介导的人HSC归巢的细胞和分子机制。因此，拟议的研究将确定一种新的方法，研究人类HSC归巢，可以潜在地提供一个基础，为化疗或全身照射后的干细胞移植的新策略的发展。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The cholinergic system is involved in regulation of the development of the hematopoietic system.

DOI：
10.1016/j.lfs.2007.04.017
发表时间：
2007-05
期刊：
Life sciences
影响因子：
6.1
作者：
Naira Serobyan;S. Jagannathan;I. Orlovskaya;I. Schraufstatter;M. Skok;J. Loring;S. Khaldoyanidi
通讯作者：
Naira Serobyan;S. Jagannathan;I. Orlovskaya;I. Schraufstatter;M. Skok;J. Loring;S. Khaldoyanidi

Visualization of the hematopoietic microenvironment: an alternative approach using the dorsal skinfold chamber model.

造血微环境的可视化：使用背侧皮褶室模型的替代方法。