HSC-精品医学课件
造血干细胞移植 ppt课件
• BMT的意义 • BMT每个入无菌层流室的护理
–无菌层流室的准备：
• 100级空气层流洁净室 • 严格的清洁、消毒和灭菌 • 空气细菌学检测达标
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护理
• 病人入无菌层流室的护理
–病人的准备
–轻度GVHD：无病生存率 –重度GVHD：无病生存率
• 病人年龄及一般情况
–年龄欲小，疗效愈好
• 预处理方案
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方法
• 供体的选择
–人白细胞抗原（HLA）配型相和程度 –血缘关系：同基因、异基因 –非血缘关系：HLA相和个数；年轻、男性、 ABO血型相和、CMV阴性
• 供者的准备：
–采集量、采集方法留观 or 住院
• 心理准备
–评估 –帮助提前熟悉环境 –提供相应指导
• 身体准备
–相关检查：组织配型、ABO血型、脏器功能、巨细胞病毒等 –清除潜在感染灶：皮肤粘膜、口腔、五官、肺部等 –肠道和皮肤准备：入室前3天－口服肠道抗生素；入室前1天 －修建指（趾）头、毛发、肚脐；入室当天洗必泰沐浴，穿 无菌衣裤，皮肤细菌培养 –灭菌饮食
造血干细胞移植 (HSCT)
ppt课件
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教学目标
• 掌握
– – 造血干细胞移植的义 造血干细胞移植后的并发症预防和应对 造血干细胞移植的分类 造血干细胞移植的准备，无菌层流室的护理，输 注的护理 造血干细胞移植的适应症 造血干细胞移植的方法 ppt课件
•
熟悉
– –
•
了解
– –
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定义
• 造血干细胞移植：hematopoietic stem cell transplantation, HSCT • 通过对受体进行预处理（照射、化疗、 免疫抑制剂），将正常供体或自体造血 干细胞经血管输注给受体，使之重建正 常的造血和免疫功能
造血干细胞移植精品医学课件
感染控制
阐述对于发生感染的患者，如何通过病原体检测、抗菌 药物治疗和免疫调节等手段控制感染。
其他并发症：GVHD以外的挑战与对策
移植后淋巴增殖性疾病：阐 述其发生原因、临床表现和 诊断方法，介绍针对该并发 症的放射治疗和化学治疗等 。
移植相关血栓性微血管病： 解析其发病机制、危险因素 和防治措施，讨论如何通过 药物治疗和血浆置换等手段 控制病情。
预处理方案制定
移植前患者需接受一系列的预处理方案，包括化疗、放疗等，以抑制患者的免疫系统、清 空骨髓空间，为供体细胞的植入创造有利条件。预处理方案的制定需根据患者的病情、年 龄、身体状况等因素进行个性化设计。
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造血干细胞移植的手术过程与后 期管理
预处理：清髓与免疫抑制治疗
清髓治疗
使用高剂量化疗药物或全身放疗，摧毁患者 自身的造血系统和免疫系统，为接受移植做 好准备。
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利用iPSCs技术生成造血干细胞，解决供体来源不足的问题，并
降低免疫原性。
新策略
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GVHD风险的降低
通过更精确的HLA配型、T细胞去除或免疫抑制药物的应用，降低移植
后移植物抗宿主病（GVHD）的发生率和严重程度。
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提高移植成功率
优化预处理方案，减少移植相关的并发症，提高造血干细胞的植入率。
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个体化治疗方案
根据患者的遗传背景、疾病状态和免疫状态，制定个体化的移植方案，
提高治疗效果。
展望
发展方向
继续探索新的基因编辑技术和细胞治疗方法，并将其应用于造血干细胞移植；同时，开展多中心、大样本的临床研究 ，以验证新技术和新策略的安全性和有效性。
挑战
在技术层面，需要解决基因编辑的精确性、安全性和效率等问题；在临床转化方面，需要解决供体来源不足、移植后 免疫排斥和复发等问题。
造血干细胞ppt课件
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特征
※造血干细胞有两个重要特征：
其一，高度的自我更新或自我复制能力；
其二，可分化成所有类型的血细胞。
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分裂方式
正常情况下，造血干细胞经过不对称性有丝分 裂成两个子代细胞。其中一个仍维持造血干细胞的 全部特征，即自我更新(self-renewal)。自我更新 使得干细胞池的大小(干细胞数量)和质量维持不变， 因而又称为自我维持(self-maintenance)。另一个 子细胞可能由于基因表达模式发生改变而使得细胞 特征出现变化，从而逐步走上分化的道路。
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在干细胞不同的分化阶段，有不同的表面标志表 达，故不同的表面标志已成为区分造血干细胞分化 阶段的重要标志。 祖细胞的表面标志为CD34+ Lin+ ，谱系特异性 抗原包括粒系CD11、13、15、16；单核系CD14；B淋 巴系CD19、20、21、22；T/NK系CD2、11、25、7、 56；红系CD47、59、71；巨核系CD31、41、42、61、 63、107等。
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继1988年第一例应用人类脐带血移植治疗贫血症成功后，脐 带血因其免疫抗原性较弱的特点，被认为是极具潜力的自骨 髓来源和外周血来源后，第三种造血干细胞移植的来源。值 得一提的是，输入的造血干细胞的数量多少，是影响造血干 细胞移植成功率的因素之一。临床应用表明输入的量越大， 成功移植率越高。“纽约血液中心”（NYBC）的国家脐带 血库报道的异基因脐带血造血干细胞移植的参考标准为0.7～ 10×107/kg。同时，脐血移植中有核细胞数量不是一个影响 疗效的独立因素，HLA完全相合可以补偿细胞数量低的影 响。。
造血干细胞移植-精品医学课件
异基因HSCT是指供体与受者基因 型不完全相同的HSCT，主要适用 于急性白血病、恶性淋巴瘤、多发 性骨髓瘤等。
移植的适应症与分类
适应症
HSC移植可用于治疗多种血液系统疾病，如恶性血液病、遗 传性疾病、自身免疫性疾病等。其中，恶性血液病是最常见 的适应症之一。
分类
根据供体与受者的关系，HSC移植可分为自体HSCT、同基因 HSCT和异基因HSCT。其中，自体HSCT具有操作简单、免疫 排斥反应低等优点，已成为临床常用的一种移植方式。
基因治疗
针对遗传性疾病和恶性肿瘤的基因缺陷，通过基因编辑技术对HSC进行基因治疗 ，以达到根治疾病的目的。
HSC在再生医学和其他领域的应用前景
再生医学
HSC具有多向分化潜能，可分化为多种细胞类型，为再生医学中组织损伤修复和器官再造等研究领域提供了新的思路。
肿瘤免疫治疗
通过HSC负载肿瘤抗原，刺激免疫反应，提高肿瘤免疫治疗的疗效和降低免疫排斥反应。
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HSC移植的基本原理和技术
HSC的分离和采集
分离方法
密度梯度离心法、免疫磁珠法、流式细胞术等，根据不同的采集部位和患者 情况选择合适的方法。
采集部位
一般为髂后或髂前上棘，也可以采集外周血。
预处理和照射
预处理
清除患者的免疫细胞，为植入的HSC创造更好的生长环境，常用药物有环磷酰胺 、ATG等。
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HSC移植的疗效和风险
疗效的评价指标和影响因素
评价指标
主要包括生存率、复发率、移植相关死亡率、移植后并发症 发生率等。
影响因素
主要包括患者的年龄、性别、疾病类型和分期、供者的选择 、HSC来源、预处理方案、GVHD预防和治疗等。
HSC-精品医学课件
，人工智能在医疗中的应用
医疗数据挖掘
通过数据挖掘技术，分析医疗大数据，为疾病诊断和治疗提供参 考和支持。
智能辅助诊断
通过深度学习和图像识别等技术，实现疾病的辅助诊断和治疗方 案的制定。
健康管理
通过可穿戴设备和智能家居等技术，实现健康管理和预防保健， 提高人们的健康水平和生活质量。
，远程医疗技术
远程会诊
消化内科
消化系统疾病的诊断和治疗。
神经内科
神经系统疾病的诊断和治疗。
外科
普通外科
包括阑尾炎、甲状腺疾病等的诊断和治疗 。
神经外科
脑部疾病的诊断和治疗，如脑瘤等。
胸外科
胸部疾病的诊断和治疗，如肺癌等。
心外科
心脏疾病的诊断和治疗，如冠心病等。
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医学诊断与治疗方法
医学诊断方法
临床诊断
通过问诊和体格检查，了解患者症 状和体征，为进一步检查和治疗提 供依据。
实验室诊断
通过血液、尿液、粪便等实验室检 查，检测出潜在的疾病指标和异常 表现。
影像学诊断
利用X线、CT、MRI等影像技术， 观察人体内部结构和病变情况。
病理学诊断
通过活检组织病理学检查，对病变 组织进行细胞和分子水平的分析。
治疗方法
药物治疗
手术治疗
根据病情选择合适的药物，通过抑制或消除 病因，减轻症状和促进康复。
通过远程会诊技术，实现专家医 生和患者之间的远程交流和治疗 ，方便患者获得更好的医疗服务 。
远程监控
通过远程监控技术，实现对患者 的实时监测和健康管理，及时发 现和处理病情。
移动医疗
通过移动医疗技术，实现医疗服 务的普及和便民化，提高医疗服 务的覆盖率和效率。
免疫细胞：造血干细胞(HSC) PPT课件
LSC继续分 化为T细胞、B 细胞和NK细胞。
MSC 进 一 步分化为单核巨噬细胞、DC 细胞、中性粒 细胞、嗜酸性 粒细胞、嗜碱 性粒细胞、肥 大细胞、红细 胞和血小板。
HSC发 育为成熟免 疫细胞的每 一阶段均需 多种细胞因 子参与。
免疫细胞分化过程
造血干细胞移植
将正常HSC输入经超剂量放、化疗的患者 体内，替代原有病理性或缺陷的造血干细胞， 重建其造血和免疫功能。
适应症：
恶性血液疾病 重症免疫缺陷 放/化疗后造血支持
遗传性疾病 某些自身免疫病
造血干细胞移植包括： 骨髓移植 外周血干细胞移植 脐血移植
骨髓移植：
20世纪50年代开始使用。HSC存在于扁骨、 不规则骨和长骨两端的红骨髓，为采集600ml骨髓， 需给供者局部麻醉，经多次骨穿才能完成。
前突然查出患白血病，第 三军医大学新桥医院的专家待其分娩后，用该产 妇父亲“骨髓和外周血”HSC+婴儿出生时采集 的脐带血对白血病进行联合移植治疗，获得成功。
造血干细胞与基因治疗
HSC是导入外源基因理想的靶细胞：
HSC具有自我更新能力，可在患者体内长期存 活并表达外源基因产物；
通过造血干细胞“动员”技术，使骨髓 HSC进入外周血，采集分离约200ml外周血 即可获得足够数量HSC并用于移植。
脐血移植：
脐带血是胎儿娩出、脐带结扎并离断后 残留在胎盘和脐带中的血液，含有可以重建 人体造血和免疫系统的HSC，可用于移植。
脐血移植的优势：
来源丰富、取材简单； 对供受体HLA相符的要求相对较低； 不易受病毒或残留肿瘤细胞污染； HSC增殖和自我增殖能力强； 脐血T、B细胞相对不成熟，GVHD发生率低； 脐血NK和LAK细胞多，有利于GVL； 脐血含基质细胞，能提供HSC生长的微环境。
血液内科ppt课件可编辑全文
五、实验室检查Ⅰ
1. Hb↓，小细胞低色素性贫血 （MCV＜80fl、MCHC＜32%)，形态
2. 骨髓：增生活跃，以晚幼红细胞为主， 幼红细胞偏小、胞浆量少。 亚铁氰化钾(普鲁士蓝反应)染色： 外铁（－），内铁（铁粒幼细胞） ↓~0，﹤15%（最常用的方法）。
存铁耗尽(iron depletion, ID), 继之红细胞内铁缺 乏(iron deficient erythropoiesis, IDE), 最终引起 缺铁性贫血(Iron deficient anemia，IDA). IDA 是铁缺乏症(包括ID, IDE和IDA)的最终阶段, 表 现为缺铁引起的小细胞低色素性贫血及其他异 常。
一、血细胞的生成
造血干细胞（hemapoietic stem cell , HSC) 起源于卵黄囊中胚层干细胞，胚胎
形成后HSC主要在胎肝，出生后4周，骨 髓成为主要的造血器官，外周血含少量 HSC，脐带血含量较多.
HSC：是各种血细胞与免疫细胞的起源 细胞.
HSC的主要特点
⑴ 自我复制：维持恒定的干细胞量； ⑵ 多方向分化、成熟：维持血 中各类细胞的数量； ⑶ 基本免疫标志：CD34+， 随分化成熟而消失， CD34+细胞占骨髓有核 细胞的1％，在外周血 约占0.05%。
含铁血黄素是铁蛋白部分变性、部 分被溶酶体作用分解的降解物，不溶于 水，不容易被利用。
（六）铁的排泄
正常情况下，人体每天铁的排泄不超 过1㎎。主要是随肠道粘膜脱落细胞由粪 便中排出。随泌尿道上皮细胞及随皮肤 细胞或出汗时排泄的铁量极少。哺乳的 母亲每天从乳汁中约排出1 ㎎铁。
（七） 铁的需要量
成年男性及绝经期女性： 1mg /d （补充生理丢失量）
造血干细胞移植-精品医学课件
重点提示
造血干细胞定义 造血干细胞的特性 造血干细胞移植分类 造血干细胞来源 ABO血型不相合的造血干细胞移植分为主侧不
合、次侧不合、主次侧不合 ABO主侧不相合造血干细胞移植患者输血时血
型的选择原则是输入的红细胞应和供者、受者 血浆相合；输入的血小板、血浆应与供者、受 者红细胞相合
多自体HSCT
多减低剂量预处 理方案的异基因 HSCT
越来越多的儿童 无关供者移植的 首选
造血干细胞移植(HSCT)的特点
❖ 供受者之间HLA配型要求严格，HLA相合者 ABO血型不一定相合；
❖ 移植患者因接受放/化疗预处理，在造血和免 疫系统重建前，需要输注血液成分和制品进行 支持治疗；
❖ 输入血液制品须经γ射线辐照，灭活其中淋巴 细胞的活性，预防输血相关移植物抗宿主病 (TA-GVHD)。
O
潜在的问题
受者体内存在针对供者红细 胞抗原的抗-A，使来源于供 者干细胞中的红细胞溶血
ABO次侧不合 O
A
供者体内存在针对受者红细
胞抗原的抗-A，因而供者骨
髓中或移植后产生的抗-A导
致受者红细胞溶血
造血干细胞移植(HSCT)的输血
原则：尽量减少溶血的发生和不必要的血型抗 体（凝集素）输入
➢ 应用成分输血 ➢ 应用辐照血液制品 ➢ 应用巨细胞病毒血清阴性的血液制品
造血干细胞疾病
重型再生障碍性贫血 镰形细胞贫血、重型珠蛋白生成障碍性贫血等
免疫缺陷疾病：重症联合免疫缺陷病等 急性放射病 对化疗敏感的实体瘤
HSCT分类
按照干细胞来源：自体造血干细胞移植 同基因造血干细胞移植 异基因造血干细胞移植
按照干细胞采集部位:骨髓造血干细胞移植 外周血造血干细胞移植 脐血干细胞移植
医学生理学课件 cellular physiology
Peter Agre, (Nobel Prize 2003)
6
Passive transport
• Facilitated diffusion
• Water-soluble substances can passively diffusion through the plasma membrane mediated by special membrane proteins down their electrochemical gradient.
• Voltage gated channels: • Chemically gated channels: • Mechanically gated channels:
• Character:
• High speed • Selection • Gated channels
• Example: Na+, K+, Ca2+
specialized organelles dispersed throughout a gelatin-like liquid, the cytosol.
• Cells are the bridge between molecules and humans.
2
Basic organization of cell membrane and transport
• Character:
• Specificity: • Saturation: • Competition:
• Example: glucose, amino acid
HSC-精品医学课件
hsc-精品医学课件xx年xx月xx日CATALOGUE目录•医学基础知识•临床医学•预防医学•医学前沿•.2.1干细胞的基本概念和分类CATALOGUE 目录•.2 .2再生医学的未来展望•.3 人工智能在医学领域的应用•.3 .1人工智能的基本概念和发展历程•.3 .2人工智能在医学影像诊断和治疗中的应用01医学基础知识从古埃及、古希腊到中国古代医学的发展历程。
医学发展史古代医学从文艺复兴到现代医学的重要事件和代表人物。
近代医学20世纪医学的重大突破和最新进展。
现代医学医学基础知识人体各系统、器官的形态、位置及相互关系。
人体解剖学生理学病理学药理学人体各器官、系统的生理功能及调节机制。
疾病发生的原因、机制、病理变化及结局等基本概念。
药物的作用机制、疗效及不良反应等基本知识。
02临床医学内科包括感冒、肺炎、慢性阻塞性肺疾病等呼吸系统疾病包括高血压、冠心病、心肌梗死等循环系统疾病包括胃炎、消化性溃疡、肝炎等消化系统疾病包括糖尿病、痛风、骨质疏松等内分泌与代谢性疾病包括骨折、软组织损伤、伤口感染等创伤与感染包括胃肠肿瘤、肠梗阻、阑尾炎等胃肠外科包括胆囊炎、胰腺炎、肝硬化等肝胆胰脾外科包括尿路结石、前列腺增生、肾癌等泌尿外科外科妇产科包括子宫肌瘤、卵巢囊肿、子宫内膜异位症等妇科疾病妊娠与分娩月子护理与新生儿养育妇科肿瘤包括早孕反应、孕期保健、分娩过程等包括产后恢复、母乳喂养、新生儿护理等包括宫颈癌、卵巢癌、子宫内膜癌等儿科包括感冒、咳嗽、发烧等常见疾病小儿内科包括先天性畸形、骨折、软组织损伤等小儿外科包括小儿手足口病、小儿肺炎等小儿感染与免疫包括营养不良、肥胖症、生长发育迟缓等小儿营养与生长发育03预防医学1流行病学23介绍流行病学的定义、原理和研究方法，包括描述性、分析性和实验性流行病学。
流行病学原理阐述疾病在时间、空间和人群中的分布特征，分析这些特征对流行病学研究的影响。
疾病分布特征介绍病因推断的基本原则和标准，包括休谟因果模型和穆尔堡因果模型等。
HSC 造血干细胞的介绍
Lecture 1 Hematopoiesis1. Introduction2. Ontogeny of hematopoiesis3. Description of the Hematopoietic Stem Cell (HSC)4. The concept of the stem cell niche5. Anatomical description of the stem cell niche6. Functional description of the stem cell niche7. Role of lineage-specific Growth Factors in hematopoiesis8. The formation of mature blood elements: 1. Myelopoiesis1. E rythrocytes2. G ranulocytes3. P latelets9. The formation of mature blood elements: 2. Lymphopoiesis1. T cells2. B cells3. N K cells10. Bone Marrow Failure1. I nherited disorders2. A cquired disorders1. IntroductionThe formed elements of the blood, such as red cells, white cells and platelets, play a vital role in the normal functioning of any human being. They are the end product of a highly specialized tissue calle d the bone marrow, which resides in the cavities of all bones of the body. The process through which formed elements of the blood are produced is called Hematopoiesis. Hematopoiesis can be envisioned as a hierarchical progression of multipotential hematopoietic stem cells that gradually lose one or more developmental options. They then become stem or progenitor cells committed to a single lineage.These single lineage progenitor cells then mature into the corresponding types of mature formed elements of the blood, also called peripheral-blood cells.As we will see in the following chapters, the bone marrow can be divided into two major cellular compartments:1. One composed with hematopoietic stem cells (HSCs) which have two major physiological properties: A.Self renewal which is essential for the maintenance of life-long hematopoiesis, and: B Differentiation into committed progenitors. 2. The other composed of multipotent progenitor cells, which cannot renew, but rather divide and differentiate into all mature formed elements of the blood.At first glance, the fact that the bone marrow tissue resides in the bone cavities of all bone does not imply that the bone itself has any role in the process of hematopoiesis. As a matter of fact, the mechanisms of bone and blood formation have traditionally been viewed as distinct unrelated processes. Compelling evidence now suggests that they are intertwined. It has been observed for a long time that HSCs are not randomlydistributed in the bone marrow tissue. In fact, they reside in close proximity to endosteal surfaces of the bone. It was therefore hypothesized that the osteoblasts, the main bone forming cells, and therefore not only the HSCs, play a central role in the process of hematopoiesis. The close intimacy of the HSC and the bone endosteal surfaces is at the origin of the concept of the Stem Cell Niche which we will discuss in detail later on. Therefore it seems that normal hematopoiesis relies on the complicity of osteoblasts and HSCs.The purpose of this lecture is to review in detail the basic physiological aspects of hematopoiesis, and discuss briefly some bone marrow failure mechanisms.2. Ontogeny of HematopoiesisHematopoiesis begins in blood islands located in extra embryonic tissues (fetal yolk sac) in the first trimester and in the aorto-gonad-mesnenophros (AGM) region. At approximately 6 weeks of gestation, hematopoiesis occurs predominantly in the fetal liver. Beginning at midterm, the medullary cavity gradually replaces the fetal liver as the main site of hematopoiesis. In some species, such as the mouse, the spleen isa major site of hematopoiesis in the adult.The yolk sac is membranous sac attached to an embryo, providing early nourishment in the form of yolk in primitive mammals and functioning as the circulatory system of the human embryo before internal circulation begins. The primitive yolksac participates in nutrient exchange between the fetal and maternalcirculations before the formation of the placenta.Figure 1: Primitive yolk sacThe yolk sac is an extra embryonic structure responsible for the initial and transient production of red cells in the embryo, mainly during the first two weeks of gestation. Before placental circulation is established, the yolk sac constitutes the primary source of exchange between the mother and the embryo (between 7-11 weeks = 7mm in diameter) and constitutes the very first site of hematopoiesis. The first blood cells observed in the embryo are large nucleated erythroblasts generated in blood islands of the extra embryonic yolk sac. Theseunique red cells have been termed primitive because of their resemblance to nucleated erythroblasts of non-mammalian species. It is now widely assumed that hematopoiesis in the yolk sac is primitive and that definitive hematopoiesis has its origins in the aorta/gonad/mesonephros (AGM) region. The first maturing blood cells and committed progenitors are provided by the yolk sac, allowing survival until AGM-derived hematopoietic stem cells can emerge, seed the liver and differentiate into mature blood cells. Stem-cell activity in the human yolk sac has not been reported. The AGM is a region of embryonic mesoderm that develops during embryonic development and is the site of origin of the definitive HSC. It has an intra embryonic location(as opposed to extra embryonic for the yolk sac) and is the site of residence and amplification of the definitive hematopoietic stem cells that eventually seed the fetal liver and adult bone marrow (see figure 2).Figure 2: The embryonic Aorto-Gonad-Mesonephros (AGM) regionInitiation of hematopoietic stem cells (HSC) in the aorta-gonad-mesonephros (AGM) region in 10- day embryos is observed with additional expansion and migration to the fetal liver (FL). In the adult mouse, both the spleen (SP) and bone marrow (BM) have hematopoietic activity.At approximately 6 weeks of gestation, hematopoiesis occurs predominantly in the fetal liver. Yolk sac hematopoietic cells are largely a transient embryonic population and the definitive stem cell, in fact, derives from AGM region. Beginning at midterm, the medullary cavity gradually replaces the fetal liver as the main site of hematopoiesis.Figure 3: Summary of the ontogeny of hematopoiesisFigure 3 shows the chronological description and respective sites of hematopoiesis during the development of a human being.3. Description of the Hematopoietic Stem Cell (HSC).Hematopoietic stem cells (HSCs) are a subset of bone marrow cells that are capable of self-renewal and of terminal differentiation into all types of mature formed elements of the blood (see figure 4). The HSC “niche”, the in vivo regulatory microenvironment where HSCs reside, and the mechanisms involved in controlling the number of adult HSCs will be discussed laterEach day an adult produces approximately 200 billionerythrocytes, 100 billion leukocytes, and 100 billion platelets. Moreover, these rates can increase by a factor or 10 or morewhen the demand for blood cells increases. All this production relies on the presence of an adequate number of HSCs.In the haematopoietic system, HSCs are heterogeneous with respect to their ability to self-renew. Multipotent progenitors constitute 0.05% of bone-marrow cells, and can be divided into three different populations: long-term self-renewing HSCs (LT-HSC) short-term self-renewing HSCs (ST-HSC) and multipotent progenitors (MPP) without detectable self-renewal potential (see figure 4). These populations form a lineage in which the long-term HSCs give rise to short-term HSCs, which in turn give rise to multipotent progenitors.As HSCs mature from the long-term self-renewing pool to multipotent progenitors, they progressively lose their potential to self-renew but become more mitotically active. Whereas long-term HSCs give rise to mature hematopoietic cells for the lifetime of the mouse, short-term HSCs and multipotent progenitors reconstitute lethally irradiated mice for less than eight weeks.Figure 4Description of the HSC compartment with LT-HSC, ST-HSC and the multipotential progenitor compartment (MPP). Blood-cell development progresses from a hematopoietic stem cell (HSC), which can undergo either self-renewal or differentiation into ST-HSC and the multipotential progenitor cells (MPP). MPP give rise to two major multilineage committed progenitor cells: a common lymphoid progenitor (CLP) or a common myeloid progenitor (CMP). These cells then give rise to more-differentiated progenitors ultimately giving rise to unilineage committed progenitors for B cells NK cells T cells granulocytes monocytes erythrocytes and platelets.HSCs cannot undergo normal somatic mitotic activity as any other kind of cells in the body as illustrated in figure5.Figure 5Symmetrical division during normal mitotic activity.If it would, then, by definition, by giving rise to two identical daughter cells trough symmetrical division would exhaust the HSC pool. In order to maintain a constant the pool of long-term HSCs an individual stem cell has to give rise to two non-identical daughter cells, one maintaining stem-cell identity and the other becoming a differentiated cell by divisional asymetry. There are two mechanisms by which this asymmetry can be achieved, depending on whether it occurs pre- (divisional asymmetry), or post- (environmental asymmetry) cell division.Figure 6Asymmetrical division in HSCs in the bone marrowAs shown in figure 6, in a, cell-fate determinants are asymmetrically localized to only one of the two daughter cells, which retains stem-cell fate, while the second daughter cell differentiates. In b, during environmental asymmetry, after division, one of two identical daughter cells remains in the self-renewing niche microenvironment while the other relocates outside the niche to a differen t, differentiation-promoting microenvironment.Maintenance of long-term HSCs and regulation of their self-renewal and differentiation is thus maintained through asymetrical division.The main characteristis of HSC are their quiescent state. They divide infrequently and can be quiescent for weeks or even months. They also are very few in numbers, representing 0.05% of all bone marrow cells.Finally, they are the only cells able so self-renew for ever, for life-time, and able at the same time to give birth to cells that will divide and mature into formed elements of the blood.4. Concept of the Hematopoietic Stem Cell niche.HSCs reside in the cavity of long and axial bones. As we will see, they are surrounded by a special microenvironment defined as the stroma. The stroma is composed of cells derived from mesenchymal stem cells (MSCs), which give rise to a mixture of cells including fibroblasts, adipocytes, endothelial cells and osteoblasts. Each of these stromal cells is essential for supporting the HSCs in their physiological role.Hematopoiesis cannot occur alone and needs all these cell partners forming the microenvironment or niche.This is where the concept of a HSC niche comes into play. As we will see, in the niche, the osteoblasts play the most important role in supporting hematopoiesis.A stem-cell niche can be defined as a spatial structure in which HSCs are housed and maintained by allowingself-renewal in the absence of differentiation. The stem-cell niche functions include storage of quiescent stem cells,self-renewal and inhibition of differentiation. The main function of a self-renewing niche would be to guarantee that by environmental and/or divisional asymmetry, one of the two daughters of a dividing stem cell maintains the stem-cell fate while the other produces differentiating progenitors.In that niche, HSCs are in intimate contact with bone, more specifically, in close proximity to bone surfaces (endosteal surfaces), supporting the concept of an endosteal niche (see figure 7)Bone marrow niche organization showing that the HSCs are not randomly distributed in the bone cavity but rather concentrated and attached to the endosteal surfaces of the bone, more specifically to osteoblasts.The more mature progenitor cells tend to localize in the middle of the cavity.The mechanisms of bone and blood formation have traditionally been viewed as distinct, unrelated processes, but compelling evidence suggests that they are intertwined. Based on observations that HSCs reside close to endosteal surfaces of the bones as shown in figure 7, it was hypothesized that osteoblasts play a central role inhematopoiesis. We will see that osteoblasts are critical in the regulation of hematopoiesis and are one of the most important regulatory cells in the stem cell niche. To put it very simply, “no osteoblasts, no hematopoiesis”. Several animal modelsstrongly implicate osteoblasts in hematopoiesis by virtue ofcreatinga niche. In mice with a maturational arrest of osteoblasts, there is a total lack of bone marrow throughout theentire skeleton and therefore total absence of hematopoiesis.5. Anatomical description of the Hematopoietic Stem Cell niche.Where do we find the HSCs niches that are so important for maintaining hematopoiesis for life by virtue of their protective effect on LT-HSCs? If one looks carefully at the anatomical aspects bones in general, including long bones, there is a special area called spongy bone or cancellous bone (see figure 8). For long bones, cancellous bone is at the epiphysis.Figure 8Anatomical schema of a long bone with spongy or “cancellous bone” at the epiphysis this is the anatomical area where most LT-HSCs reside in contact with osteoblasts in a close network of trabecula (see text). This type of bone (spongy or cancellous) is mostly found in the axial skeleton. As shown in figure 3, the axial skeleton is the major site of hematopoiesis in the adult.Cancellous bone is a spongy type of bone with a very high surface area, found at the ends of long bones and axial bones (vertebrae). The very high surface area is the result of a complex network of trabecula, which are fine bone spicules. The spicules form a latticework, with interstices filled with bone marrow where LT-HSC are in intimate contact with osteoblasts and other mesenchymal cells such as adipocytes, endothelial cells and fibroblasts (see figure 9).Figure 9Anatomy of the HSC niche in the cancellous or spongy bone with the presence of a network of trabeculae creating multiple spaces thereby increasing the surface area where HSCs can come in intimate contact with osteoblasts and provide life-long hematopoiesisIn the HSC niche, although the survival of HSCs requires intimate cell-cell contact with osteoblasts, one must remember that bone marrow stromal cells derived from mesenchymal stem cells, including fibroblasts, adipocytes and endothelial cells are also important in supporting HSCs by secretion of important survival proteins. In summary, the main anatomical site of the HSC niche is in the spongy or cancellous bone where one finds a significant increase in bone surface area ensuring and increase and adequate number of LT-HSCs. As we will see, the control of the HSC numbers is directly related to the number of osteoblasts.By increasing the bone surface area (by the same token the number of osteoblasts) through the network of bone trabecula, there is a parallel increase in the number of LT-HSCs. In the adult, the spongy or cancellous bone is found mainly at the proximal ends of the humerus and femur, in the vertebrae, ribs, sternum and pelvis.6. Functional description of the Hematopoietic Stem Cell niche.The functions of the niche include adhesive interaction between HSCs and the niche.Although, as stated earlier, four different stromal cells interplay within that niche, such as adipocytes, endothelial cells, fibroblasts and osteoblasts, the major function of the HSC ni che is to regulate the number of HSCs through a complex interaction with osteoblasts. This is why HSCs localize close to the endosteallining of bone-marrow cavities in trabecular regions of long bones, whereas more differentiated hematopoietic progenitors are found mainly in the central bone-marrow region (see figure 7). Quiescent HSCs detach from the endosteal niche and migrate towards the centre of the bone marrow to the vascular zone from where they establish hematopoiesis. This specific site (center of the bone marrow) is mostly populated with endothelial cells, fibroblasts and adipocytes. It is called the vascular niche, as opposed to the endosteal niche. Collectively, the vascular and endosteal niches strongly cooperate to control HSC quiescence and self-renewing activity (and therefore HSC numbers), as well as the production of early progenitors to maintain homeostasis or re-establish it after injury.The main functions HSCs niches are to store HSCs, ensure their self renewal and inhibit their differentiation. As stated earlier, HSCs are in intimate contact with bone (osteoblasts), and cell–cell contact is responsible for the apparently unlimited proliferative capacity and inhibition of maturation of HSCs. Mice with defects in osteoblast differentiation and consequent failure to form bone have defective bone marrow hematopoiesis.An increase in the number of osteoblasts directly correlates with the number of functional LT HSCs, indicating that osteoblasts are an essential part of the endosteal niche and are limiting for niche size and/or activity.Figure 10Epiphysis of a normal mouse (WT) and a mouse that has been engineered (Tg) to produce more bone. There isa significant increase in the network of trabeculae (bone spicules) in the engineered mouse correlating withan increase in the LT-HSCs numbers.In summary, the main function of the endosteal niche where mos t fibroblasts are found is to protect LT-HSCs, maintain a critical number by inhibiting apoptosis and unnecessary differentiation toward more mature progenitors. Absence of this crucial function would lead to a depletion of the LT-HSC pool and bone marrow failure.The main function of the vascular niche is to support and promote the differentiation and maturation of more mature progenitors into the well known formed elements of the blood through secretion of different proteins (growth factors→ see next section) by stromal cells (see figures 11 and 12).Figure 11Anatomical distribution of the endosteal and vascular niches. The endosteal niche provides control on LT-HSC quiescence, numbers and function while the vascular niche promotes differentiation and maturation of multipotent progenitors (MMP) toward mature elements of the blood.Figure 12Bone marrow biopsy specimen showing the histological aspect of the endosteal and vascular niches.7. Role of specific Growth Factors in hematopoiesis.1. GeneralHematopoiesis is under the influence several regulatory proteins, such as hematopoietic growth factors (HGFs).HGFs are chemicals, generally cytokines and interleukins that interact with developing immature marrow progenitor cells and lead to greater numbers of red cells, white cells, or platelets, or combinations of these.Erythropoietin(EPO) is the main growth factor responsible for the production or mature red cells. While hypoxia stimulates (EPO) production by the juxtatubular interstitial cellsof the renal cortex, T-lymphocytes, endothelial cells, fibroblasts, and monocytes/macrophages from the bone marrow stroma are the source of the other HGFs. The locations of the genes responsible for the main HGFs are known: chromosome 7 for erythropoietin (EPO); the long arm of chromosome 5 for granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), macrophage colony-stimulating factor (M-CSF), and the M-CSF receptor;and chromosome 17 for granulocyte colony-stimulating factor (G-CSF). The review of all HGFs involved in the formation of mature blood elements is beyond the scope of this lecture. I will restrict the description to only 3 of them: EPO, G-CSF, and thrombopoietin (TPO).2. How they workHGFs bind to surface receptors of progenitor cells and act as intracellular mediators. They are essential for the survival and proliferationof hematopoietic cells at all stages of development, and therefore to the production of the formed element of the blood. Some growth factors influence the proliferation and maturation of multilineage progenitors, (IL-3, IL-7) while others affect only cells committed to single lineage maturation (EPO, G-CSF) (see figure 14). Each lineage needs a specific growth factor.HGFs first attach or bind to a transmembrane protein called the receptor, on the surface of the target progenitor cell. This receptor has one or two extracellular bindingdomains a transmembraneand an intracellular domain. The moment the protein (cytokine or interleukin or growth factor) binds to its receptor, it triggers activation of the cell with ensuing proliferation and maturation.Figure 13Mechanism of action of growth factors. In A, the receptor with 2 extracellular domains, in yellow and green, and one intracellular domain in white. In B, the growth factor blue oval is bound to the receptor.IL-3 (Interleukin-3) is a growth factor that acts early, possibly even at the level of the pluripotent stem cell (see figure 14), to induce formation of nonlymphoid cells (erythrocytes, monocytes, granulocytes (neutrophils, eosinophils, basophils, and megakaryocytes). On the other hand, IL-7 - induces the differentiation of lymphoid progenitor into B progenitor and T. Erythropoietin (EPO) induces terminal erythrocyte development and regulates RBC production. Macrophage colony-stimulating factor (M-CSF) and granulocyte colony-stimulating factor (G-CSF) promote the formation of monocytes and granulocytic cells, respectively.Figure 14A schematic representation of growth factor cellular targets. IL-3 acts early, at the level of the common myeloidprogenitor (CMP) to induce formation of the nonlymphoid cells (erythrocytes, monocytes, gran ulocytes [neutrophils, eosinophils, basophils], and megakaryocytes). IL-7 is responsible for the differentiation of the common lymphoid progenitor (CLP) into mature B,T, and NK cells. EPO and G-CSF act at a later stage of development, on unipotential progenitors.3. Erythropoietin (EPO)Erythropoietin is the favorite drug of the bikers from the “Tour the France”. No wonder, EPO induces terminal erythrocyte development and regulates RBC production and therefore tissue oxygenation.. The juxtatubular interstitial cellsof the renal cortex, which produce approximately 90 percentof the erythropoietin in blood sense oxygen levelsand triggers erythropoietin formation. Erythropoietin promotes the proliferation of erythroid progenitorcells by reducing the level of cell-cycle inhibitors and supports their survival by increasingan anti antiapoptosis protein. Elimination of the erythropoietingene or its receptor in mice causes severe anemia and death. The administration of erythropoietin to animals or humans increasesthe number of erythroid progenitor cells, which differentiateinto normoblasts, enucleate, and leave the bone marrow.4. Granulocyte colony-stimulating factor (G-CSF)G-CSF is a glycoprotein produced by a number of different tissues to stimulate a committed pro genitor to produce mature neutrophils. It also stimulates the survival, proliferation, differentiation, and function of neutrophil granulocyte progenitor cells and mature neutrophils. As opposed to IL-3 which affects aprogenitor cell that is multipotential, G-CSF triggers the differentiation of a progenitor cell only committed to neutrophilic differentiation and maturation. In oncology a recombinant form of G-CSF is used to accelerate recovery from neutropenia. Chemotherapy can cause myelosuppression and unacceptably low levels of neutrophils, subjecting patients to infections and sepsis.5. Thrombopoietin (TPO)Thrombopoietin is the primary regulator of platelet production. It supports the survival and proliferation of megakaryocyteprogenitors. Invitro, thrombopoietin induces the differentiation of progenitorcells into large megakaryocytes, each one capable of producingthousands of platelets. Thrombopoietin, a potent stimulatorof platelet production, causes thrombocytosis when administeredto animals or humans. In mice, elimination of thethrombopoietin gene or its receptor reduces the level of productionof megakaryocytes and platelets to approximately 10 percentof normal.8. The formation of mature blood elements: 1. MyelopoisisBy definition, myelopoisis is the process that gives rise to formed elements of the blood including red cells (erythropoiesis), platelets (thrombopoiesis) and granulocytes (granulopoiesis). These formed elements of the blood are the products of the Common Myeloid Progenitor (CMP) (see figure 14).1 ErythropoiesisFigure 15Maturational and differentiation sequence from the immature proerythroblasts to mature enucleated red cells.The maturation sequence of the progeny coming from CFU-E is the proerythroblasts, to basophilic erythroblast, to polychromatic erythroblast, to orthochromatic erythroblast to erythrocyte.Figure 16A bone marrow smear showing the maturation sequence from the proerythroblasts (1), to basophilicerythroblast (2) to polychromatic erythroblast, to orthochromatic erythroblast (3) to erythrocyte.As shown in figure 14, erythropoiesis is initiated by progenitors with a high proliferation rate called Burst Forming Units Erythroid (BFU-E) and followed by a second type of progenitors, Colony Forming Units Erythroid (CFU-E). The first identifiable cell in a bone marrow smear from maturation of CFU-E is the proerythroblast, shown in figure 16 (1).2 GranulopoiesisFor the sake of simplicity, I will briefly describe the granulocyte maturation and make no mention about the monocyte lineage. Granulopoiesis is the development of the granulocytic white blood cells, the neutrophils, the basophils and the eosinophils. Figure 17 shows the example of neutrophilic differentiation and maturation. The first identifiable precursor of the granulocytes in a bone marrow under the microscope is the myeloblast. As shown in figure 14, the Colony Forming Unit-Granulocyte (CFU-G), under the influence of GCS-F, matures into six distinct morphological stages: Myeloblast, Promyelocyte, Myelocyte, Metamyelocyte, Band, and, Segmented neutrophil ( figure 18). The neutrophil is the chief phagocytic leukocyte of the body. It has a half life of only 6hours in the blood and its main role is to migrate to sites of infection.Figure 17A description of the different stages of maturation of the neutrophilic lineage. After 5 to 6 days of maturatio n anddifferentiation in the bone marrow, the neutrophil stays only 6 hours in the circulation and then migrates to tissues.Figure 18Morphological characteristics of the different stages of maturation of the neutrophilic lineage as they appear under the microscope on a bone marrow smear: Upper left to right, the Myeloblast, Promyelocyte and Myelocyte. Lower right to left: the Metamyelocyte, Band and Mature Neutrophil.3. Thrombopoiesis.Thrombopoiesis is the process of formation of platelets from immature precursors. The normal sequence of maturation is from the early megakaryoblast (1), to the megakaryoblast (2), the mekagaryocyte (3) and finally mature platelets (4) detaching from the cytoplasm of megakaryocytes. The generation time from the LT-HSC to mature platelet production is about 10 days. As shown in figure 14, the Colony Forming Unit Megakaryocyte (CFU-Meg) gives rise to the earliest identifiable cell of this lineage which is the early megakaryoblast (no # 1 in figure 19).Figure 19Identifiable progeny of the CFU-Meg in the bone marrow: Early megakaryoblast (1), megakaryoblast (2), mekagaryocyte (3) and finally mature platelets (4).9. The formation of mature blood elements: 2. LymphopoiesisBy definition, lymphopoiesis is the process of formation of formed elements of the blood that includes T lymphocytes, B lymphocytes and Natural Killer cells. They form a crucial part of the immune system. These formed elements of the blood are the products of the Common Lymphoid Progenitor (CLP) (figure 14). It is beyond the scope of this lecture to describe in detail the lymphopoiesis. We will concentrate on general issues.The lymphocytes as all hemopoietic cells are derived for the HSCs which differentiate into cells common for the two lymphocytic series, B and T-cells (CLP). The CLP divides into precursors pro-B and pro-T cells, (figure14) which develop into mature B- and T-lymphocytes. As shown in figure 20, the site of development andmaturation of B lymphocytes is in the bone marrow. As for T lymphocytes, the pro-T-cells leave the bone marrow and the process of development and maturation of T cells occurs in the thymus. Once the B。
造血干细胞与造血干细胞移植模板ppt课件
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（一）造血干细胞（HSC）的起源
▪ 胚胎2周时 卵黄囊 4周时 胚肝 5个月时 骨髓 出生后 骨髓 成年人HSC主要分布在红骨髓、脾脏及淋 巴结。
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（二）造血干细胞的表面标志
▪ 1. CD34 造血细胞的一种重要标志 ▪ CD34+细胞占骨髓细胞的1%~4%
▪ 2. CD117 是干细胞生长因子受体， IgSF 成员，
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▪ ㈢ 未累及骨髓的疾病
▪ 如非原发于骨髓的恶性实体肿瘤、自身免 疫性疾病等。
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▪ ㈣遗传代谢性疾病
▪ 先天性免疫缺陷病、粘多糖病、先天性造 血异常症
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四、HSCT治疗步骤
▪ ▪ 1 选择合适的病例 ▪ 上述疾病患者中,经过临床治疗或病情分析
已 ▪ 经明确,通过常规手段无法获得理想疗效,
▪ ㈣间充质干细胞移植 ▪ 骨髓基质细胞的前体
▪ ㈤混合造血干细胞移植
▪ 具有异基因造血干细胞移植的移植抗瘤效 应（GVT）及自体干细胞移植不受供者限 制的优点
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二、造血干/祖细胞移植的原理
▪ 造血干/组细胞移植是经过大剂量放、化疗 或其他免疫抑制预处理，清除受体体内的 肿瘤细胞、异常克隆细胞、阻断发病机制 ，然后把自体或异体造血干细胞移植给受 体，使受体重建正常造血，重建正常免疫 ，从而达到治疗的目的的一种治疗手段
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15
▪ 主要程序
▪ ⑴应用化疗或细胞因子（G-CSF）、（ GM-CSF）有效动员骨髓干细胞
▪ ⑵用血细胞分离机采集外周血干细胞
▪ ⑶经过体外扩增，获得足够在体内重建造 血所需的干细胞
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▪ 优点 ▪ ⑴采集安全简便 ▪ ⑵造血及免疫功能恢复快 ▪ ⑶受肿瘤细胞污染机会少 ▪ ⑷采集的细胞中含有大量异体T细胞、NK
临床血液学检验ppt课件
检验医师的责任
• 要有扎实的和全面的基础医学和临床医学知识 • 能正确掌握各项有关血液疾病诊断和反映病情的试
验 • 适应血液学的发展，建立有关新试验 • 能从事有关科学研究的实验工作 • 具有一定程度的血液病临床知识，对疾病能下诊断 • 具有与临床之间进（evidence-based medicine,EBM）：寻求、 应用证据的医学，亦称实证医学、求证医学。EBM的基 本要素是证据；核心是追踪当前最好的外在证据以回答 临床解决的问题。
12
➢ 血液制品的临床应用：全血→成分血 （RBC悬液、粒细胞、血小板、血浆、丙 种球蛋白、凝血因子等）
➢ 输血存在的问题：输血不良反应；输血传 播性疾病
➢ 自体血体外循环
13
• 血液学检验的任务：利用血细胞的检验技 术、超微结构技术、病理学技术、生物化 学技术、免疫学技术、遗传学技术、细胞 生物学技术、分子生物学技术以及其他多 种技术，对血液系统疾病和非血液系统疾 病所致的血液学异常进行基础理论研究和 临床诊治的观察，从而推动和促进血液学 和临床血液学的发展和提高。
16
• 循证检验医学（EBLM）/循证血液检验医学（EBHLM）的 循证步骤：循证问题，提出要解决的问题；进行系统的文 献查阅，全面收集所有相关、可靠的大样本随机对照试验 （对照、随机分组、盲法）；应用meta分析对文献、资料 和数据进行严格的评价，评价其可靠性、真实性而得出全 面、真实的评价结果；进行调整，确定最佳方案进行临床 实践；在实践中发现新问题，对进行的临床实践做出后效 评价，发布新的结论与实践结果，指导临床实践。
• microRNA(miRNA)：一组19-24个核苷酸的非编码小 RNA，主要在转录和翻译水平调控mRNA，目前成为许多 肿瘤的诊断和预后判断的分子标志和治疗靶标
免疫细胞：造血干细胞(HSC) PPT课件
脐血T、B细胞相对不成熟，GVHD发生率低； 脐血NK和LAK细胞多，有利于GVL； 脐血含基质细胞，能提供HSC生长的微环境。
2009.02.27报道：
一名26岁产妇临产前突然查出患白血病，第 三军医大学新桥医院的专家待其分娩后，用该产 妇父亲“骨髓和外周血” HSC+ 婴儿出生时采集 的脐带血对白血病进行联合移植治疗，获得成功。
通过造血干细胞“动员”技术，使骨髓 HSC 进入外周血，采集分离约 200ml外周血
即可获得足够数量HSC并用于移植。
脐血移植：
脐带血是胎儿娩出、脐带结扎并离断后 残留在胎盘和脐带中的血液，含有可以重建 人体造血和免疫系统的HSC，可用于移植。
脐血移植的优势：
来源丰富、取材简单； 对供受体HLA相符的要求相对较低； 不易受病毒或残留肿瘤细胞污染； HSC增殖和自我增殖能力强；
适应症：
恶性血液疾病
重症免疫缺陷
遗传性疾病
某些自身免疫病
放/化疗后造血支持
造血干细胞移植包括：
骨髓移植 外周血干细胞移植 脐血移植
骨髓移植：
20 世纪 50 年代开始使用。 HSC 存在于扁骨、
不规则骨和长骨两端的红骨髓，为采集600ml骨髓，
需给供者局部麻醉，经多次骨穿才能完成。
外周血干细胞移植：
造血干细胞与基因治疗
HSC是导入外源基因理想的靶细胞：
HSC具有自我更新能力，可在患者体内长期存 活并表达外源基因产物； HSC具有多向分化潜能，分化成的转基因血细 胞可分布全身发挥效应； 多种疾病与造血细胞异常有关，将缺学家在Science上报道：
从 2 名患有严重免疫缺陷症的患儿骨髓中抽取 HSC ，以逆转录病毒为载体，将正常基因导入 其中，然后回输给病孩。经 10 个月随访，获得 较满意的效果，患儿免疫系统达到正常水平。
矿产
矿产资源开发利用方案编写内容要求及审查大纲
矿产资源开发利用方案编写内容要求及《矿产资源开发利用方案》审查大纲一、概述
㈠矿区位置、隶属关系和企业性质。
如为改扩建矿山, 应说明矿山现状、
特点及存在的主要问题。
㈡编制依据
(1简述项目前期工作进展情况及与有关方面对项目的意向性协议情况。
(2 列出开发利用方案编制所依据的主要基础性资料的名称。
如经储量管理部门认定的矿区地质勘探报告、选矿试验报告、加工利用试验报告、工程地质初评资料、矿区水文资料和供水资料等。
对改、扩建矿山应有生产实际资料, 如矿山总平面现状图、矿床开拓系统图、采场现状图和主要采选设备清单等。
二、矿产品需求现状和预测
㈠该矿产在国内需求情况和市场供应情况
1、矿产品现状及加工利用趋向。
2、国内近、远期的需求量及主要销向预测。
㈡产品价格分析
1、国内矿产品价格现状。
2、矿产品价格稳定性及变化趋势。
三、矿产资源概况
㈠矿区总体概况
1、矿区总体规划情况。
2、矿区矿产资源概况。
3、该设计与矿区总体开发的关系。
㈡该设计项目的资源概况
1、矿床地质及构造特征。
2、矿床开采技术条件及水文地质条件。
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HSC
HPC
Precursor,matured
blood cells
Multiple
limitedof HSC
3.其他特征 ★形态学上难于辨认
★高度静止90% -- 99.5%处于G0期
龄”
★高度不均一，存在“年 结构
HPC
multipotential haemetopoietic progenitor cell (mHPC) HPC committed haemetopoietic progenitor cell (cHPC)
22；红系为CD47，59，71；）
人造血干祖细胞的表型 (1)
干细胞
CD 34 + + Thy-1 + + C-kit + AC-133 + + CD 33 － CD 38 － CD 45RO －
祖细 胞
早期
晚期
++
+
+
±
+
+
++
－
+
+
+
+
+
+
人 造 血 干 祖 细 胞 的 表 型 (2)
干细胞
CFU-GM(colony forming unit-
granulocyte-macrophage)
CFU-Meg(colony forming unit-
megakaryocyte)
CFU-TL,CFU-BL(T,B-Lymphocyte)
mHPC and cHPC
• Summary
★Differentiation: multiple cell lineage → limited cell lineage → single cell lineage .
CD 34, 133, 45, 33, 2, 3, 4, 8, 14, 15, 16, 19, 20, 24
(-)
—成骨细胞 —软骨细胞 —肌腱细胞
—血管平滑肌细胞 —血管外层细胞 —血管内皮细胞
The differentiation and maturation of HSC
HSC
HPC
Precursor Matured
Differences between HSC and HPC
• HSC: unlimited self-renewal ability • HPC: limited self-renewal ability
(HSC,G0 phase)
HSC HSC HPC matured
Molecular marks of HSC
鼠植入，外周血长期出现人类髓系和淋巴系细胞，证 实为人类干细胞植入 • 人－绵羊嵌合实验
HCS的检测方法
CFU-S Assay
↖
Hematopoietic Colonies
造血干细胞移植(HSC Transplantation,HSCT)
将富含造血干细胞血液输入经特殊 处理的受体（患者），以期重新建立受 损的造血系统和免疫系统或矫正异常造 血的过程。
• CD(Cluster of differentiation)（白）细胞分化 抗原，在细胞的不同发育阶段出现
CD34+ HSC CD38-
lineage- (lineage specific antigen,
系别抗原，某个系列细胞共有的 抗原, 如，粒系为CD11，13， 15， 16； B淋巴系为CD19，20，21，
1 骨髓移植（BMT） 2 外周血造血干细胞移植（peripheral blood
hematopoietic stem celltransplantation，PBHSCT）
3 脐带血造血干细胞移植（CBHCST） 4 CD34细胞移植（CD34 T）
HSC移植分类
二、根据供者分类
1 同基因(synogeneic)
limited self-renewal (secondary colony transplantation)
mHPC and cHPC
cHPC
BFU-E(burst forming unit-erythrocyte) CFU-E (colony forming unit-erythrocyte) CFU-G(colony forming unit-granulocyte)
Characteristics of HSC
• 1. Self-renewal (or self-maintenance)
different HSC has different self-renewal abilities
★脾结节连续移植实验 ★ 骨髓连续移植实验 ★体外集落转移分析
Characteristics of HSC
HSC采集
HSC采集
• PBHSCT 1、HSC Mobilization：
① 正常成人PBSC占外周血液单个核细胞的1‰左右，经
适当动员处理可提高至10‰ ;
②动员剂
肿瘤化疗药物：如环磷酰胺、马利兰、 柔红霉素、阿糖胞苷等
造血细胞刺激因子：G-CSF、M-CSF、 GM-CSF、IL-3、IL-6和SCF等
2.multiple differentiation Concept About Differentiation
multiple differentiation
Characteristics of HSC
2.multiple differentiation Characteristics of Differentiation
绒毛 体蒂 羊膜囊 上胚层 下胚层 卵黄囊
胚外中胚 层 胚外体腔
绒毛膜
卵黄囊(yolk sac)
• 是位于胚体腹侧包围在卵黄外的具有丰富血管 的膜囊。
• 鸟类卵黄囊随胚体的增长及卵黄的消耗而逐渐 萎缩，最终被吸收，形成小肠的一部分。
• 第5周末人胚胎卵黄囊与原肠断离，逐渐退化， 至第7周成为小于5毫米的小囊，残存于胎盘表 面。
mHPC and cHPC
mHPC
LTC-IC(long-term culture-initiating cell HPP-CFC(high proliferative potential
colony-forming unit)
CFU-mix(3~5 cell lineages)
mHPC more than 3 cell lineages
祖细 胞
早期
晚期
Lin:
－
－
++
(G) CD 11, 13, 15, 16
－
－
++
(Mφ) CD 12, 14
－
－
++
(T/ NK) CD 2, 25, 7, 56, 45RA
－
－
++
(B) CD 19, 20, 21, 22, 45RB
－
－
++
(Mk) CD 31, 41, 42, 61, 107
HSC采集
• HSC Collection:
设备：CS-3000plus; MSC+血细胞分离机； 抗凝剂：枸橼酸／枸橼酸钠／葡萄糖（ACD） 采集量：MNC采集量约2×108/Kg体重，
MNC总数约1~2×1010, 血液总体积50~100ml
血细胞分离
HSC保存与运输
• 非冷冻保存:
1、冷藏保存：肝素抗凝,加适量TC199培 养液,4℃保存, 尽早使用,最高期限7天; 超过3天效果较差。
Accordingly, the self-renewal ability would be limited
mHPC and cHPC
Summary
★ Proliferation: the earlier the HPC is, the stronger proliferative ability it has, the bigger its colony would be. Accordingly, the longer the colony can be seen,the fewer the colony number would be
Hematopoietic Stem Cell and HSCT
↖
Hematopoietic Stem Cell (HSC)
• 主要存在于造血器官的、具有自我更新 （self-renewal）和多向分化潜能（multidifferentiation）,能够分化发育为各种外 周血细胞的幼稚细胞。
HSC的起源(yolk sac)
hematopoietic reconstitution immunological reconstitution
HSCT的适应症
• 血液系统恶性肿瘤
• 造血衰竭性疾病：AA，MDS等
• 非血液系统恶性肿瘤
• 其他：放射病，遗传病，自身免疫性疾病, 基因治疗载体;AIDS?等
HSC移植分类
一、根据HSC来源分类
HSC采集
• HSC Mobilization：
③动员方法：于PBSC单采前5d，皮下注射重组细胞集
落刺激因子，如G-CSF2.5～5.0μg/（kg.d）；采集当 天皮下注射较高剂量重组细胞集落刺激因子（如G-
CSF5μg/kg），直至白细胞总数达20×109/L，血小 板达20×109/L后，静脉推注地塞米松10mg后1-2h 开始单采外周血造血干细胞．一般需单采5-7 次，每次均须计数单个核细胞总数，测定 CD34+细胞百分率
• 1. Self-renewal (or self-maintenance) • Concept