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BIOLOGIC AND IMMUNOLOGIC ASPECTS OF TRANSFUSION MEDICINE

输血医学的生物学和免疫学方面

基本信息

批准号：
7689744
负责人：
Sherrill J. Slichter
金额：
$ 211.07万
依托单位：
BLOODWORKS
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 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7689744
关键词：
BIOLOGIC IMMUNOLOGIC ASPECTS TRANSFUSION MEDICINE

项目摘要

DESCRIPTION (provided by applicant): Our research focuses on several biologic and immunologic aspects of transfusion medicine. Three projects deal with questions related to platelet biology. Specifically, Dr. Slichter's project seeks to define the parameters that must be met to allow extension of platelet storage by evaluating the effects of an initial collection injury that may limit storage duration and the role of storage solutions in facilitating extended platelet storage. Dr. Gilligan and Reems' project expects to identify the optimal methods of growing megakaryocytes in culture with the goal of producing platelets or "platelet-like fragments" that function similarly to platelets in maintaining hemostasis. Dr. Josephson's project focuses on the development of foamy virus vectors as a gene transfer system to deliver therapeutic genes into hematopoietic stem cells. The target disease that he will use as a model for his system is congenital amegakaryocytic thrombocytopenia (CAMT). Two additional projects have an immunologic emphasis. Dr. Nelson's project involves transfusing three different types of blood products [standard (unmodified), leukoreduced, or leukoreduced gamma-irradiated] into immunocompetent patients undergoing open-heart surgery. The differences in serologic and cellular immune responses in the three patient cohorts as well as the influence of HLA Class II sharing between donors and recipients on immunologic outcomes will be evaluated. Dr. S. Pratt and Thompson's project addresses issues related to the prevention or reversal of inhibitor antibody formation in patients with acquired or congenital hemophilia A. Modification of T-cell epitopes in FVIII may lead to non-immunogenic FVIII replacement therapy while new peptides or recombinant proteins may be useful in tolerance induction for patients with existing antibodies. Finally, an administrative core will be used to maintain an interactive environment among the SCCOR scientists and provide administrative and statistical support. In summary, we have utilized the established expertise of our scientists to address several important questions in Transfusion Medicine. In addition, most projects involve the skills of one or more Blood Center scientists working within and between the projects to accomplish the objectives of this SCCOR Program. (End of Abstract) PROJECT 1: Strategies to Extend Platelet Storage (Slichter, Sherrill) DESCRIPTION (provided by applicant): The primary objective of these studies is to determine whether platelets (plts) can be stored for longer than the currently-licensed 5 days. Furthermore, does the duration of plt storage depend on the type of plt product being stored (apheresis plts, plt concentrates prepared from plt-rich plasma (PRP), or from buffy coats (BC), pre-storage pooled PRP plt concentrates, or pathogen-reduced apheresis or BC plts), and the medium used for storage; i.e., plasma or a storage solution. The four critical questions that will be addressed in our studies are: 1) does the method of plt collection using apheresis procedures versus preparing plt concentrates from whole blood influence storage duration?; 2) does pre-storage pooling of plt concentrates affect plt viability?; 3) do plt storage solutions allow plts to be stored longer than plts stored in plasma?; and 4) can pathogen-reduced plts be stored for extended time periods similar to non-pathogen reduced plts? Although in vitro tests will be performed to document post-storage plt counts as well as a variety of assays to determine post-storage plt function, metabolism and apoptosis, the post-storage quality of the extended stored plts will be based on in vivo measurements in normal volunteers and thrombocytopenic patients. Specifically, radiolabeled plt recovery and survival measurements of extended stored autologous plts in normal volunteers will be used to determine post-storage plt viability for all types of plt products stored in plasma versus a storage solution. For plts that are stored for longer than 8 days and/or are stored in a storage solution, transfusion studies in the thrombocytopenic patients will be used to evaluate plt viability by measuring the radiolabeled recovery and survival of the donors' plts following transfusion. Alternatively, patient responses to transfused donor plts will be determined by measuring post-transfusion plt increments, corrected count increments, and days-to-next transfusion. Plt function (i.e., hemostasis) following the transfusion of extended stored donor plts will be monitored by plt count versus bleeding time measurements and by radiochromium-labeled stool blood loss studies. At the conclusion of these studies, we should know how long each type of plts can be stored in plasma or Plasmalyte, the relative merits of each type of plts, and whether the extended stored plts are both viable and functional when given to thrombocytopenic patients. (End of Abstract)

描述（由申请人提供）：我们的研究集中在输血医学的几个生物学和免疫学方面。三个项目涉及与血小板生物学有关的问题。具体而言，Slichter博士的项目旨在通过评估可能限制储存时间的初始采集损伤的影响以及储存溶液在促进延长血小板储存中的作用来确定延长血小板储存必须满足的参数。 Gilligan博士和Reems博士的项目希望确定培养巨核细胞的最佳方法，目的是产生血小板或“血小板样片段”，其功能与维持止血的血小板相似。Josephson博士的项目集中在泡沫病毒载体的发展，作为一种基因转移系统，将治疗基因传递到造血干细胞中。他将用作其系统模型的目标疾病是先天性无巨核细胞性血小板减少症（CAMT）。另外两个项目的重点是免疫学。纳尔逊博士的项目涉及使用三种不同类型的血液制品[标准（未修饰），白细胞减少，或白细胞减少γ辐射]到免疫功能正常的患者接受心脏直视手术。将评价三个患者队列中血清学和细胞免疫应答的差异以及供体和受体之间HLA II类共享对免疫学结局的影响。Dr. S. Pratt和Thompson的项目解决了与获得性或先天性血友病A患者中抑制抗体形成的预防或逆转相关的问题。 FVIII中T细胞表位的修饰可能导致非免疫原性FVIII替代疗法，而新的肽或重组蛋白可能用于对具有现有抗体的患者的耐受性诱导。最后，一个行政核心将用于维持SCCOR科学家之间的互动环境，并提供行政和统计支持。总之，我们已经利用我们科学家的专业知识来解决输血医学中的几个重要问题。此外，大多数项目涉及一名或多名血液中心科学家在项目内部和项目之间工作的技能，以实现本SCCOR计划的目标。(End摘要）项目1：延长血小板储存的策略（Slichter，Sherrill）描述（由申请人提供）：这些研究的主要目的是确定血小板（plt）是否可以保存超过目前许可的5天。此外，plt储存的持续时间是否取决于储存的plt产品的类型（单采plt、从富含plt的血浆（PRP）或从血沉棕黄层（BC）制备的plt浓缩物、储存前合并的PRP plt浓缩物或病原体减少的单采或BC plt）和用于储存的介质;即，血浆或储存溶液。我们的研究将涉及四个关键问题：1）使用单采术采集血小板的方法与从全血中制备血小板浓缩物的方法是否影响储存时间？2)血小板浓缩物的储存前合并是否影响血小板活力？3)PLT储存溶液是否允许PLT储存的时间长于PLT储存在血浆中的时间？和4）病原体减少的PLT可以类似于非病原体减少的PLT储存延长的时间段吗？尽管将进行体外试验以记录储存后plt计数以及各种测定以确定储存后plt功能、代谢和细胞凋亡，但延长储存的plt的储存后质量将基于正常志愿者和血小板减少患者的体内测量。具体而言，将使用放射性标记的正常志愿者中延长储存的自体plt的plt回收率和存活率测量值来确定储存在血浆中与储存溶液中的所有类型plt产品的储存后plt活力。对于储存超过8天和/或储存在储存溶液中的plt，将使用血小板减少患者的输血研究，通过测量输血后供体plt的放射性标记回收率和存活率来评价plt活力。或者，通过测量输血后plt增量、校正计数增量和下一次输血的天数来确定患者对输血供体plt的反应。 Plt函数（即，止血）将通过PLT计数对出血时间的测量和通过放射性铬标记的粪便失血研究来监测。在这些研究的结论中，我们应该知道每种类型的血小板可以在血浆或Plasmalyte中储存多久，每种类型血小板的相对优点，以及当给予血小板减少症患者时，延长储存的血小板是否既有活力又有功能。(End摘要）

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Extended storage of autologous apheresis platelets in plasma.

DOI：
10.1111/vox.12010
发表时间：
2013-05
期刊：
Vox sanguinis
影响因子：
2.7
作者：
Slichter SJ;Bolgiano D;Corson J;Jones MK;Christoffel T;Pellham E
通讯作者：
Pellham E

Effects of pretransfusion warming of platelets to 35 degrees C on posttransfusion platelet viability.

输血前将血小板升温至 35 摄氏度对输血后血小板活力的影响。

DOI：
10.1111/j.1537-2995.2009.02313.x
发表时间：
2009
期刊：
Transfusion
影响因子：
2.9
作者：
Slichter,SherrillJ;Christoffel,Todd;Corson,Jill;Jones,MaryKay;Pellham,Esther;Bolgiano,Doug
通讯作者：
Bolgiano,Doug

Distinct functional effects for dynamin 3 during megakaryocytopoiesis.

动力蛋白 3 在巨核细胞生成过程中具有独特的功能作用。