Manufacturing USA: Biomanufacturing of Cell Microparticles from Stem Cells As Novel Thrombotic Therapeutic Agents

美国制造：利用干细胞生物制造细胞微粒作为新型血栓治疗剂

基本信息

批准号：
1804741
负责人：
Eleftherios Papoutsakis
金额：
$ 50万
依托单位：
University of Delaware
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2023-07-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1804741&HistoricalAwards=false
关键词：
Manufacturing USA Biomanufacturing Cell Microparticles

项目摘要

Cell and gene therapies can be used to treat a large array of diseases. Therapy is based on using whole cells or viruses to deliver genes or proteins to the patient. Membrane sacs, known as extracellular vesicles (EVs), are a promising new delivery system. They can target specific types of cells for delivery of their cargo, and can carry proteins, fats and ribonucleic acids. This project will develop EV technology based on specialized cells in the bone marrow that generate platelets. Development of this technology could lead to new strategies for solving long-standing problems in Transfusion Medicine by providing a stable and abundant source of platelets. High school and college students from underrepresented groups will engage in research experiences to stimulate their interest in engineering and biomanufacturing careers. The goal of this project is to develop foundational science and engineering for preparing functional extracellular vesicles (EVs) to enable novel cell and gene therapies. EVs are submicron membrane vesicles that carry RNAs, proteins and lipids from their parent cells. Cells use EVs to communicate with other cells, delivering signals through their content, and targeting a rather narrow range of cell types through receptor-recognition mechanisms based on surface proteins. It is now widely accepted that extracellular vesicles are excellent candidates for enabling safe and potent cell and gene therapies. This project will focus on megakaryocytic microparticles (MPs; a type of extracellular vesicles), which target and deliver cargo to hematopoietic stem & progenitor cells (HSPCs). The most important feature of these MPs is that they specifically target HSPCs and program them to generate more megakaryocytes, the precursors of platelets. This project will develop characterization methods and assays for these MPs so that they can be used to develop robust protocols for generating large MP quantities. Finally, the project will also assess the biological efficacy of these MPs as thrombotic agents using a simple murine model.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

细胞和基因疗法可用于治疗大量疾病。治疗基于使用全细胞或病毒向患者输送基因或蛋白质。膜囊，称为细胞外囊泡（EV），是一个有希望的新输送系统。它们可以靶向特定类型的细胞以输送货物，并可以携带蛋白质，脂肪和核糖核酸。该项目将基于产生血小板的骨髓中的专门细胞开发EV技术。这项技术的开发可能会导致新的策略，以通过提供稳定且丰富的血小板来源来解决输血医学长期问题。来自代表性不足的团体的高中和大学生将参与研究经验，以刺激他们对工程和生物制造职业的兴趣。该项目的目的是开发用于制备功能外囊泡（EV）的基础科学和工程，以实现新颖的细胞和基因疗法。电动汽车是携带来自母细胞的RNA，蛋白质和脂质的亚微米膜囊泡。细胞使用电动汽车与其他细胞进行通信，通过其含量传递信号，并通过基于表面蛋白的受体识别机制靶向相当狭窄的细胞类型。现在广泛接受的是，细胞外囊泡是实现安全，有效的细胞和基因疗法的出色候选物。该项目将集中于巨核细胞微粒（MPS；一种类型的细胞外囊泡），该囊泡靶向并将货物运送到造血茎和祖细胞（HSPC）。这些MP的最重要特征是它们专门针对HSPC并编程它们以生成更多的巨核细胞，即血小板的前体。该项目将开发这些MPS的表征方法和测定方法，以便它们可以用于开发可实现大量MP数量的强大协议。最后，该项目还将使用简单的鼠模型评估这些国会议员作为血小板剂的生物学功效。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的智力优点和更广泛的影响评估标准来评估的。