Tissue Engineering of Hematopoietic Bone

造血骨组织工程

基本信息

批准号：
7880481
负责人：
Karen Kemper Hirschi
金额：
$ 17.39万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-30 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7880481
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

项目摘要

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）：我们的长期目标是设计造血骨外体，以治疗骨骼和造血的疾病。该应用的具体目标是产生含有多能骨髓的骨骼，可重复的干细胞可以满足患者的长期再生需求，并为修复骨缺损的修复提供结构完整性。 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生物成像（Barry and Sevick，BCM和米饭）。我们的总体假设是导致骨骼形成以及功能性骨髓和脉管系统的建立的步骤在从头形成的模型中是可辨认的，并且可以定义。此外，通过了解此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和体内概括多能HSC HSC的传播，从而在体内概括造血骨形成。为了解决这些假设，我们建立了一种从头骨形成的模型，在体内产生了血管化的，充满骨髓的骨骼的模型，并证明在该骨结构中形成的骨髓可以使功能性HSC的存活和繁殖能够长期重新结合所有血细胞谱系。我们已经开始解剖并定义了导致造血骨形成的分子步骤，并建立了跟踪骨髓衍生细胞的命运和功能所需的生物成像技术。我们设计并生成的生物材料将使细胞存活和繁殖能够，并容易制造骨骼和血管的生物反应器。在此应用中，我们将将所有这些成分集成到工程造血骨骼，并在体外和体内测试其功能。此外，我们已经建立了与BCM和水稻技术转让办公室的必要联系，以促进我们对生物技术和临床环境的研究过渡。