Tissue Engineering of Hematopoietic Bone

造血骨组织工程

• 批准号: 7675424
• 负责人: Karen Kemper Hirschi
• 金额: $ 111.17万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7675424
• 关键词: Address; Algorithms; Biocompatible Materials; Biological Models; Biology; Biomedical Engineering; Bioreactors; Blood Cells; Blood Vessels; Bone Development; Bone Diseases; Bone Marrow; Bone Regeneration; Cell Lineage; Cell physiology; Cells; Clinic; Clinical; Defect; Development; Disease; Engineering; Engraftment; Environment; Event; Fluorescence; Goals; Grant; Hematopoiesis; Hematopoietic; Hematopoietic stem cells; Human; Image; In Vitro; Kinetics; Lead; Link; Marrow; Measurement; Medicine; Mentors; Modeling; Molecular; Monitor; Motivation; Mus; Organ; Osteogenesis; Patients; Perfusion; Photons; Population; Postdoctoral Fellow; Process; Production; Proteins; Publications; Reporter; Reporter Genes; Research; Research Personnel; Rice; Specific Pathogen Frees; Stem cells; Structure; Students; System; Techniques; Technology Transfer; Testing; Tissue Engineering; Transillumination; Vascularization; Work; animal facility; base; bioimaging; blood treatment; bone; bone engineering; cell type; college; design; germ free condition; in vivo; insight; luminescence; meetings; migration; prevent; progenitor; programs; reconstitution; regenerative; reparative medicine; skills; stem cell biology

DESCRIPTION (provided by applicant): Our long-term goal is to engineer hematopoietic bone ex vivo to treat disorders of both bone and hematopoiesis. The specific goal of this application is to produce bone that contains marrow with pluripotent, repopulating stem cells that can fulfill the long-term regenerative needs of patients, as well as provide structural integrity for the repair of bone defects. To achieve this goal, we have assembled a team of interactive investigators from Baylor College of Medicine (BCM) and Rice that have the required expertise in biology and engineering, which includes: hematopoiesis and stem cell biology (Goodell, BCM), bone development (Davis, BCM), vascular development (Hirschi, BCM & Rice), biomaterials and bioreactors (West and Mikos, Rice) and bioimaging (Barry and Sevick, BCM and Rice). Our overarching hypotheses are that the steps that lead to bone formation and the establishment of functional marrow and vasculature are dissectible and definable in a model of de novo bone formation; furthermore, by understanding the sequence and kinetics of the cellular and molecular events needed for this process, we will gain insight into how to recapitulate hematopoietic bone formation ex vivo for the propagation of pluripotent HSC in vitro and in vivo. Toward addressing these hypotheses, we have established a model of de novo bone formation in which vascularized, marrow-filled bone was generated in vivo, and demonstrated that the marrow formed within this bone structure enables the survival and propagation of functional HSC that are capable of long-term reconstitution of all blood cell lineages in vivo. We have begun the dissect and define the molecular steps that lead to hematopoietic bone formation and have established bioimaging techniques needed to track the fate and function of marrow-derived cells ex vivo and in vivo. We have designed and generated biomaterials that will enable cellular survival and propagation, and bioreactors in which bone and blood vessels are readily fabricated. In this application, we will integrate all of these components to engineer hematopoietic bone and test its functions in vitro and in vivo. Furthermore, we have established necessary links to BCM and Rice technology transfer offices to facilitate the transition of our research into biotech and clinical settings.

描述（由申请人提供）：我们的长期目标是离体改造造血骨以治疗骨和造血功能障碍。该应用的具体目标是生产含有骨髓和多能再生干细胞的骨骼，可以满足患者的长期再生需求，并为修复骨缺损提供结构完整性。为了实现这一目标，我们从贝勒医学院 (BCM) 和莱斯组建了一支互动研究人员团队，他们拥有所需的生物学和工程专业知识，其中包括：造血和干细胞生物学（Goodell，BCM）、骨骼发育（戴维斯，BCM）、血管发育（Hirschi、BCM 和 Rice）、生物材料和生物反应器（West 和 Mikos，Rice）以及 生物成像（Barry 和 Sevick、BCM 和 Rice）。我们的总体假设是，导致骨形成以及功能性骨髓和脉管系统建立的步骤在从头骨形成模型中是可分割和定义的；此外，通过了解这一过程所需的细胞和分子事件的序列和动力学，我们将深入了解如何在体外重现造血骨形成，以实现多能 HSC 在体外和体内的增殖。为了解决这些假设，我们建立了一种从头骨形成模型，其中在体内生成血管化、充满骨髓的骨，并证明在这种骨结构内形成的骨髓能够使功能性造血干细胞存活和繁殖，而功能性造血干细胞能够在体内长期重建所有血细胞谱系。我们已经开始剖析和定义导致造血骨形成的分子步骤，并建立了跟踪离体和体内骨髓来源细胞的命运和功能所需的生物成像技术。我们设计并生产了能够实现细胞存活和繁殖的生物材料，以及易于制造骨骼和血管的生物反应器。在此应用中，我们将整合所有这些组件来设计造血骨并在体外和体内测试其功能。此外，我们还与 BCM 和 Rice 技术转让办公室建立了必要的联系，以促进我们的研究向生物技术和临床环境的转变。