转化医学与输血科研

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转化医学与输血科研
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赵树铭
教授, 主任医师
医学博士
博士研究生导师
第三军医大学西南医院输血科
从事专业: 输血医学
专业任职:
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中国输血协会理事
全军血液管理专业委员会理事
中国临床输血专业委员会常务委员
重庆市输血协会副理事长
美国血库协会会员
国际输血协会会员
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教学目的
 熟悉
* 转化医学与输血医学热点
 了解
 新技术\新方法
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教学内容
转化医学与输血医学特点
输血医学-我的思考?
美国输血医学的科研课题
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输血医学
 定义:研究血液及其成分(包括生物制品)治疗
有关疾病,防治输血不良反应及并发症(包括
输血传播疾病)的一门多学科的临床应用学科
。这门学科是集中运用医学和技术手段研究
血液及其成分(包括生物制品)如何安全、有
效地输给患者,使患者受益。
-中国输血医学常用术语
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TRANSUFION MEDICINE
In actuality, there is no
single basic science
discipline of transfusion
medicine; instead basic
science research in
transfusion medicine cuts
across a multitude of
fields including genetics,
molecular biology, cell
biology, biochemistry,
immunology and virology.
实际上,输血医
学不是单一基础
性科学学科,包
含了遗传学、分
子生物学、细胞
生物学、生物化
学、免疫学和病
毒学等多学科的
综合学科
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输血医学的特点
 采供血机构及其管理
献血管理
 献血者的征集与管理
 血液样品的采集及检验
 血液成分的研制及质量控制
 血型及配血
血液研究
 HLA分型及组织相容性试验
 外周血保存
 骨髓和脐血干细胞分离与保存
 血液代用品研制
 输血指征和各种成分血适应证
 自身输血
临床输血
 治疗性血液成分单采
 输血相关疾病和输血并发症及其预防
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输血医学的特点
基础研究的成果转化成为实际应用,
“从实验台到病床旁”
Bench to Bedside,简称B2B
1992年,美国《科学》杂志;
1996年,在著名医学杂志《柳叶刀》上,第
一次出现了“转化医学”这个新名词
转化医学应该是B2B2B,即从实验室到病
床,再从病床回到实验室
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输血医学的成功案例
nucleic acid testing for infectious
disease agents 核酸试验
the use of monoclonal antibodies in
immunohematology 单抗血清
the transfusion of pathogen
inactivated platelet and plasma
products 血小板和血浆的病原体灭活
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NAT
基础研究的工具,在短短不到10年内被
用于血液病原体筛查
美国FDA、重要商业公司、NIH国立心肺-血液研究所
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病原体灭活研究
 基础科学研究--试剂和投送
 体外研究--证实灭活多种传染性病原体的效果
 动物毒理学实验
 I 和 II期临床试验--证明在健康自愿者中的安全性
 III期扩大的临床试验--证实安全性以及效果
 产品制备的认可
 常规血液中心制备的设备和条件,甚至定价等
 由于对受血者接受血液后产生未知副作用的疑虑,
还需在多个国家进行临床回顾性监督调查
药物开发
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动物模型研究中仍存在的科学问题
 red cell alloimmunization红细胞同种免疫
 graft versus host disease移植物抗宿主病
 transfusion related immunomodulation输
血相关的免疫调理
 transfusion related acute lung injury输血
相关的急性肺损伤
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输血输血科学问题
 红细胞同种异体免疫反应、GVHD、TRALI
 常规是验证在良好控制的动物模型中的特定科学
假说,再应用这些研究成果去设计对受血者的临
床和流行病学研究
 对一个科学假说的验证需要从基础研究、动物实
验以及结合临床试验的结果等获得广泛的信息才
能确立
科学研究基本原
则
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探索临床使用产品的最适指征
输血治疗的广泛性
血液成分的复杂性
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美国临床输血科研
 输血医学和血细胞发育临床试验网项目
Transfusion Medicine ⁄ Hemostasis Clinical
Trials Network (TMH CTN),包括了美国17家医
学中心或医院和一家数据处理中心
多中心临床试验
对血液病-肿瘤患者的血小板输注剂量试验
心血管外科病人的不同库存期红细胞的输
注效果研究
干细胞移植后的败血症患者的粒细胞输注
研究
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输血医学及其特点
输血医学-我的思考?
美国输血医学的科研课题
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输血医学 - 我的思考?
 献血者招募
 献血者病原体检测
 血型血清学规范化(反定型)
 稀有血型血液输注的原则和实践(Rh阴性血)
 大剂量输血原则与临床效果
 疑难血型与交叉配血(不规则抗体、电子交叉配血)
 血液成分制备的标准化(去白、辐照、冷冻、手工分
血小板、24hFFP)
 细胞治疗的规范化(输血科、医生、研究员)
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输血医学研究热点
血型血清学规范化(反定型)
 操作规范化
– 复核问题
– 签名问题
 试剂规范化
– 反定型试剂
关于红细胞ABO血型鉴定规范化的思考及建议. 中国输血杂志,2009,22(6):431-43209
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输血医学研究热点
血型血清学规范化
 疑难血型鉴定
 抗体筛查
个体化输血治疗与电子交叉配血. 中国输血杂志,2012个体化输血治疗与电子交叉配血.doc
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输血医学研究热点
血液成分制备的标准化(去白、辐照、
冷冻、手工分血小板、24hFP)
制备成分后保存质量、时间、临床效果
操作规范、指南(计划?)
赵树铭.转化医学与输血医学. 中国输血杂志,2011,24(10):831-83211
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输血医学研究热点
细胞治疗的规范化(输血科、医生、研
究员)
项目种类:CIK、DC、SC
操作规范(计划?)
质量保证
赵树铭. 细胞治疗的研究进展. 中国输血杂志,2010,23(2):79-8510\输血专题-.pdf
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输血医学研究热点
血液治疗
临床需求:血浆置换、血脂去除、血小板胶、
血液成分去除
操作规范
质量保证
赵树铭. 重庆地区输血医学现状与发展策略. 重庆医学,2009,38(12):141709cq
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输血医学研究热点
输血科智能与自动化
– 血型与配血 – 电子交叉配血
– 输血副反应 – 预警系统
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输血医学及其特点
输血医学-我的思考?
美国输血医学的科研课题
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2011年AABB资助输血医学研究课题
Bondanza, MD, PhD
H San Raffaele Scientific Institute
Cell Therapy Of Multiple Myeloma By
Genetic Redirection Of T Cells Against
Cd44v6
基因定向改造抗Cd44v6 的T细胞治疗多发性骨
髓瘤
Multiple myeloma, a cancer arising from plasma cells, is the
second most common hematologic malignancy, constituting 1
percent of all cancers. Clinical experience with long-term
survival after allogeneic HSC transplantation suggests that
promising results against multiple myeloma may be achieved
through a T cell-mediated immunologic mechanism. Bondanza
and colleagues propose to conduct preclinical validation of a
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novel cell therapy strategy for multiple myeloma treatment based
 Mettine H.A. Bos, PhD
Leiden University Medical Center, Einthoven Laboratory
for Experimental Vascular Medicine
Mechanisms Regulating the Macromolecular
Enzyme Complex Assembly in Blood Coagulation
 血液凝固过程中调节巨分子酶复合物形成的机制
 Clotting factors are integral to the blood coagulation
process, and disorders in clotting factors can lead
to life threatening bleeding disorders. In some cases,
clotting factors work together, such as the enzyme
factor X and its cofactor, factor V. Bos and
coworkers propose to investigate the molecular
mechanisms that regulate the assembly of enzymecofactor complexes driving blood coagulation.
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 Swapan Kumar Dasgupta, PhD
Baylor College of Medicine
Signaling Cascade Leading to Phosphatidylserine Exposure in
Stored Platelets
 储存血小板中导致磷脂酰丝氨酸暴露的信号级联反应
 Stored platelets undergo changes collectively referred to as the
platelet storage lesion. One of the changes is the exposure of the
anionic phospholipid phosphatidylserine, or PS, on the cell surface,
a hallmark of apoptosis (cell death). Platelets exposing PS are
rapidly cleared from circulation, suggesting that this exposure is a
signal that prompts macrophages to rid the body of these cells.
Dasgupta and colleagues propose that inhibiting PS exposure may
help increase the storage time and in vivo recovery of stored
platelets.
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 Eldad A. Hod, MD
Columbia University Medical Center
Effect of Repeat Blood Donation on Atherosclerosis and
Cancer Risk in Murine Models
 重复献血对大鼠模型中动脉粥样硬化形成和癌症危险的影响
 The long-term effects of blood donation on certain disease
processes are unknown; however, some researchers have
suggested that donation may be cardioprotective and others
have proposed that it may reduce the risk of development of
certain cancers. Hod will use a mouse model of blood
donation that he previously developed to further investigate
whether there may be benefits of phlebotomy over time. Hod
and colleagues propose to test two hypotheses: that frequent
donation is protective, the apoE-knockout mouse model of
atherosclerosis and the p53 heterozygous mutant mice that
are prone to develop tumors.
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 Katherine C. MacNamara, PhD
Albany Medical College
IFNγ-Mediated Control of Hematopoietic Stem and
Progenitor Cell Differentiation
 造血干细胞和多能干细胞分化过程中干扰素γ介导的调控作用
 Interferon-gamma, or IFN-gamma, is a cytokine known for
being a suppressor of hematopoiesis. However, recent
studies suggest that its roles in the blood system are
more complex. Based on her earlier research, MacNamara
postulates that IFN-gamma acts differently in less
differentiated cells — hematopoietic stem cells and
progenitor cells — than in more mature cells, where most
previous research on its activity has been conducted.
With this NBF grant, MacNamara and colleagues propose
to determine the molecular mechanisms that regulate IFNgamma signaling in distinct populations of HSCs and
progenitor cells.
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 Nilam S. Mangalmurti, MD
University of Pennsylvania
Role of Red Cell Advanced Glycation End products in
Endothelial Dysfunction
 内皮功能失衡过程中红细胞严重糖化终未产物的作用
 Observational studies have found that transfusion of stored red
blood cells is associated with multiple adverse outcomes,
including increased length of hospital stay, prolonged time on
ventilator, infections and mortality. Lung injury, independent of
transfusion-related acute lung injury, can occur in critically ill
patients receiving RBCs. Mangalmurti and colleagues have
recently shown that one consequence of RBC storage may be
the formation of advanced glycation end-products, or AGEs, on
erythrocyte membranes, and that RBCs that have undergone
AGE modification can induce oxidative damage in lung cells
through a receptor for AGE. With this NBF grant, she proposes
to investigate the mechanism of AGE formation on RBCs and
look for ways to prevent it.
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其它问题?
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