In vitro bioreactor sys for platelet formation

用于血小板形成的体外生物反应器系统

• 批准号: 8723656
• 负责人: DAVID L. KAPLAN
• 金额: $ 32.94万
• 依托单位: TUFTS UNIVERSITY MEDFORD
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8723656
• 关键词: Address; Adhesions; Alpha Granule; Apoptosis; Area; Attention; Automobile Driving; Biochemical; Bioreactors; Blood Platelet Disorders; Blood Platelets; Blood Vessels; Bone Marrow; Capsid Proteins; Cell Maturation; Cells; Clinical; Clinical Treatment; Collagen; Collagen Type IV; Collection; Data; Development; Disease; Electron Microscopy; Engineering; Environment; Fibrinogen; Fostering; Gel; Goals; Healthcare; Hemostatic Agents; Housing; Human; In Vitro; Inflammatory; Integrin alpha2beta1; Integrins; Investigation; Laboratories; Lead; Megakaryocytes; Megakaryocytopoieses; Membrane; Microtomy; Modeling; Modification; Molecular; Morphology; Nutrient; Outcome; Oxygen; Oxygen measurement, partial pressure, arterial; Pathogenesis; Pathologic; Pathway interactions; Patients; Physiological; Platelet Activation; Platelet Transfusion; Porosity; Positioning Attribute; Procedures; Process; Production; Proteins; Role; Signal Transduction; Silk; Source; Supporting Cell; Surface; System; Thick; Thrombus; Tissue Model; Tissues; Transmission Electron Microscopy; Tube; Vascular blood supply; base; bone; cell motility; design; functional outcomes; hydrophilicity; improved; innovation; insight; migration; novel; programs; receptor; success; von Willebrand Factor

DESCRIPTION (provided by applicant): Millions of platelet transfusions are conducted each year, yet the supply of this blood component is limited, thus patient access to treat disorders is problematic. There are also many diseases where platelet production or function are impaired, resulting in severe consequences and where there are limited clinical options available. To address these current limitations, new modes to generate functional platelets in vitro would provide a major benefit to many patients, as well as provide an approach to permit the systematic investigation of mechanisms involved in functional platelet formation. Our goal in this Project is to build upon our recent successful studies where a novel bioreactor system was engineered to house megakaryocytes (Mks) and to generate functional platelets in vitro. We will exploit this system to address our hypothesis; engineered microenvironments in vitro can be tailored to optimize the formation of functional platelets. To address the needs in the program we will: (Aim 1) establish a bioreactor-based 3D tissue system to study the mechanisms of Mk development and platelet release, with functional outcomes in terms of functional platelets generated and recovered from the system, and (Aim 2) to use this 3D tissue system to investigate mechanisms of platelet production related to biochemical signalling and environmental components (i.e. matrices, oxygen tension) as well as pathological megakaryopoiesis by including Mks from patients with platelet related diseases. With insight from this system we will be positioned to interrogate the maturation of Mks from both normal vs. diseased sources in order to begin to establish differences in Mk outcomes (adhesion, migration, proplatelet formation, platelet production and function). The outcome for the proposed study would be twofold: (1) a new laboratory model for Mk development, proplatelet formation and platelet release in normal and abnormal (disease) states, and (2) mechanistic insight into these processes. In the long run, building upon this new in vitro tissue system would allow for the more systematic understanding of the processes involved in Mk development, as well as insight into modes to intervene in disease states associated with these cells.

描述（由申请人提供）：每年进行数百万个血小板输血，但该血液成分的供应有限，因此患者使用治疗疾病是有问题的。在许多疾病中，血小板产生或功能受损，导致严重后果以及可用的临床选择有限。为了解决这些当前的局限性，在体外生成功能性血小板的新模式将为许多患者提供主要好处，并提供了一种允许系统研究功能血小板形成机制的方法。我们在该项目中的目标是建立我们最近的成功研​​究，在该研究中，一种新型的生物反应器系统被设计为容纳巨核细胞（MKS）并在体外产生功能性血小板。我们将利用该系统来解决我们的假设；可以在体外进行工程的微环境，以优化功能性血小板的形成。 To address the needs in the program we will: (Aim 1) establish a bioreactor-based 3D tissue system to study the mechanisms of Mk development and platelet release, with functional outcomes in terms of functional platelets generated and recovered from the system, and (Aim 2) to use this 3D tissue system to investigate mechanisms of platelet production related to biochemical signalling and environmental components (i.e. matrices, oxygen tension) as well作为病理性的巨核酸，包括来自血小板相关疾病患者的MK。有了该系统的洞察力，我们将定位从两种正常和患病来源的MK的成熟来询问，以便开始在MK结局（粘附，迁移，预言形成，血小板产生和功能）上建立差异。拟议的研究的结果将是双重的：（1）一种新的用于MK发育，原始骨骼形成和血小板释放的实验室模型，以及（疾病）状态（疾病）状态，以及（2）对这些过程的机理见解。从长远来看，建立在这种新的体外组织系统的基础上，将使对MK发育所涉及的过程以及对与这些细胞相关的疾病状态进行干预的模式有更系统的了解。