Biomaterials Approach to Expand Hematopoietic Cells ex vivo

离体扩增造血细胞的生物材料方法

• 批准号: 7144520
• 负责人: KAM W LEONG
• 金额: $ 36.88万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-20 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7144520
• 关键词: CD34 molecule; NOD mouse; SCID mouse; bioengineering /biomedical engineering; biological signal transduction; biomaterial development /preparation; biomaterials; biomedical equipment development; biomimetics; bioreactors; biotechnology; bone marrow; cell adhesion molecules; cell differentiation; cell growth regulation; cell proliferation; cord blood; extracellular matrix; fibronectins; hematopoietic stem cells; heparin; human tissue; surface property; tissue /cell culture; tissue support frame

DESCRIPTION (provided by applicant): Hematopoietic cells can provide benefit in a variety of clinical settings. These include cells for support of patients undergoing high-dose chemotherapy, as a target for replacement gene therapy, and as a source of cells for immunotherapy. The limitation to many of these applications has been the insufficient number of donor cells. An efficient and practical ex vivo expansion of hematopoietic progenitors (HPC) and hematopoietic stem cells (HSC) is critical in realizing the tremendous potential of HPC/HSC transplantation. The overall objective of this project is to develop a clinically relevant approach, through biomaterials engineering, to efficiently expand human hematopoietic cells. Signals emanating from the HSC niche play a crucial role in regulating the fate decision of HSC on whether to self-renew or differentiate. Extracellular matrix (ECM) components are important elements of the HSC niche. They provide the adhesive interactions between HSCs and cell adhesion molecules in the regulation of hematopoiesis in bone marrow. In hypothesizing that a favorable hematopoietic, bone marrow-like topographical microenvironment can be created by immobilizing adhesion molecules on the surface of a three-dimensional scaffold, we propose to optimize the expansion of CD34-selected as well as unselected umbilical cord blood cells (CB) in these biofunctional scaffolds. We will first establish a robust synthetic scheme of conjugating fibronectin (FN), CS1 peptide, and heparin to the surface of poly(ethylene terephthalate) (PET) scaffolds with different topographical features. After evaluating the expansion of hematopoietic cells in these scaffolds with respect to their self-renewal, differentiation, and in vivo engraftment potential, we will test the most promising scaffolds in a scaled-up culture. We propose a novel bioreactor design that will take advantage of these optimized biofunctional scaffolds by maximizing the contact area of the hematopoietic cells with the scaffolds. There has not been a systematic effort to optimize the expansion of hematopoietic cells from cord blood through a combination of biomaterials and bioreactor design. With this systematic and focused approach we aspire to develop a clinically practical strategy of efficiently expanding hematopoietic cells.

描述（由申请人提供）：造血细胞可以在各种临床环境中提供好处。这些包括用于支持接受高剂量化疗的患者，作为替代基因治疗的靶标以及作为免疫疗法的细胞来源。这些应用中许多应用的局限性一直是供体细胞数量不足。造血祖细胞（HPC）和造血干细胞（HSC）的有效而实用的离体扩张对于实现HPC/HSC移植的巨大潜力至关重要。该项目的总体目的是通过生物材料工程开发一种临床相关方法，以有效扩展人类造血细胞。 HSC利基市场发出的信号在调节HSC关于自我更新还是区分的HSC的命运决定中起着至关重要的作用。细胞外基质（ECM）组件是HSC利基市场的重要元素。它们提供了HSC和细胞粘附分子之间在骨髓中调节造血的粘附相互作用。在假设的是，可以通过将粘附分子固定在三维脚手的表面上来创建一个有利的造血，骨髓状的特形微环境，我们建议优化CD34固定的扩展以及未选择的Umbilical Corel-cortlial-cortlial-cortlical cort-libeal-colle-blood-collical cortlial-cortlical cortlial-colly-blibilical cortlial-collical cortlial-colly-blood colly comply（cb）这些内部不合适的攻击。我们将首先建立一个稳健的合成方案，即结合纤连蛋白（FN），CS1肽和肝素到具有不同地形特征的聚（乙烯二甲酸乙酯）（PET）支架的表面。在评估了造血细胞在这些支架中的扩张相对于它们的自我更新，分化和体内植入潜力的扩张，我们将测试在扩展的培养中最有希望的脚手架。我们提出了一种新型的生物反应器设计，该设计将通过最大化造血细胞与支架的接触区域来利用这些优化的生物功能支架。通过生物材料和生物反应器设计的组合，没有进行系统的努力来优化造血细胞从脐带血的扩张。通过这种系统性和专注的方法，我们渴望制定有效扩展造血细胞的临床实用策略。