干细胞治疗技术研究进展与发展趋势培训课件

美国《科学》杂志七次评出干细胞为21世纪，干细胞再生医学有希望形成巨大的健康产业美总统第13505号行政令-干细胞科研的解禁令备忘录（2009年3月11日）十大科学成果之一又一场医疗革命2015年,习近平总书记指出,“两弹一星”、多复变函数论、陆相成油理论、人工合成牛胰岛素等成就，高温超导、中微子物理、量子反常霍尔效应、纳米科技、干细胞研究、人类基因组测序等基础科学突破，为我国作为一个有世界影响的大国奠定了重要基础。2009年,温家宝总理指出：干细胞研究促进了再生医学的发展,这是继药物治疗、手术治疗之后的又一场医疗革命，我们要力争在干细胞研究的更多领域取得领先地位。

巨大的社会和经济效益预计干细胞市场在2025可达$4000亿元。Onecell,OnedreamStemcellSelf-renewDifferentiationFormtissues&organsIndividualdevelopmentmaturationandageingDifferentiationWhatarestemcells?

什么是干细胞?Stemcells:unitsofdevelopment,unitsofregeneration,andunitsinevolution.WeissmanIL.Cell.100:157–68,2000.

干细胞:机体发育、再生和进化的单元DifferentiationPotencydefinitionofstemcells–干细胞分类Totipotent(全能)

stemcellscandifferentiateintoembryonicandextraembryoniccelltypes.Pluripotent(亚全能)stemcellsarethedescendantsoftotipotentcellsandcandifferentiateintonearlyallcells,i.e.cellsderivedfromanyofthethreegermlayer.Multipotent(多能)

stemcellscandifferentiateintoanumberofcelltypes,butonlythoseofacloselyrelatedfamilyofcells.Oligopotent

(寡能)stemcellscandifferentiateintoonlyafewcelltypes,suchaslymphoidormyeloidstemcells.]Unipotent(单能)

stemcellscanproduceonlyonecelltype,theirown,buthavethepropertyofself-renewal,whichdistinguishesthemfromnon-stemcellsInducedpluripotentstemcells–诱导多能干细胞间充质干细胞(MSC)MesenchymalstemcellMesenchymalstromalcellsBlood–leukemia,anemia(AA,Fanconianemia),radiationinjuryImmunediseases–GVHD,SLE,SEVascular–Brainorheartinfarction,limbIschemiaNeural–SpinalCordInjury,Stroke,Parkinson’sdisease,Alzheimer'sDisease,Metabolic–Diabetes,liverdisordersSkeletal/Muscle–Osteoporosis,Cartilage,MusculardystrophyExcretory–Bladder/IncontinenceDermatology–Skininjury,mucosainjuryOphthalmology/Vision–retinaldisease…..Clinicalpotentialofstemcells–干细胞临床用途

内在因素环境因素DNA损伤肿瘤与干细胞干细胞衰老肿瘤组织衰老全身衰老机能衰老Relationamongstemcells,agingandcancer干细胞与衰老和肿瘤的关系免疫细胞治疗是21世纪最前沿的肿瘤治疗方法肿瘤自体细胞免疫疗法适用于多种肿瘤，包括恶性黑色素瘤、前列腺癌、肾癌、膀胱癌、卵巢癌、结肠癌、直肠癌、乳腺癌、宫颈癌、肺癌、喉癌、鼻咽癌、胰腺癌、肝癌、胃癌等.实体瘤手术后防止复发，也可以用于多发性骨髓瘤、B淋巴瘤和白血病等血液系统恶性肿瘤的复发CAR-T:医药界的阿波罗11号

0-1010-20 20-30 30-4040-5050-60>60AGEINYEARSTOTALSTEMCELLS(LOGSCALE)THENUMBEROFSTEMCELLSDECREASESBYALOGFOREVERYDECADEOFLIFEAgingandstemcelllossandsenescenceThehallmarksofAging衰老的特征Cell,2013中国干细胞治疗技术研究发展历程Before19901991-20002001-20052006-20102011-2015骨髓造血干细胞血液造血干细胞骨髓MSC胎盘脐带MSC脂肪干细胞血管干细胞其它组织干细胞胚胎干细胞诱导多能干细胞研究热点研究点papernumberNeuralstemcellsSkinstemcellsVascularstemcellsIPScellsESCGlobal

2352982097677097999861737217USA

60222614421201845253411548China

20849217565611398922705Japan

17729188766666811243444Germany

1381113384717045302279UK

99889494143124002230France

82527212892682321282Italy

9339754275582198884Canada

73257562132442141352Korea

5662715213200227890Australia

4588400124100174863Publishedpapersondifferentstemcells(TOP10)Datacollectedfrom

and（by08.31.2015)

MSCtotalBonemarrowMSCCordMSCPlacentaMSCAdiposeMSCClinicaltrialGlobal362731390219696143530530USA7566254020380596106China6895347065397413110Japan243797355342375Germany2049728772619411Italy1811690744921811Korea17445601903734846UK10753763915592France9053222499019Canada76326042104611Australia6002081126457Datacollectedfrom

and（by08.31.2015)Publishedpapersonmesenchymalstemcells(TOP10)4/7/2025

Clinicalapplicationofstemcells-干细胞临床应用神经系统疾病脊髓损伤SpinalCordInjury脑卒中Stroke脑瘫CerebralPalsy肌萎缩侧索硬化AmyotrophicLateralSclerosis帕金森病Parkinson’sDisease多发性硬化MultipleSclerosis老年性痴呆Alzheimer's

Disease免疫系统疾病系统性硬化Systemic

Sclerosis系统性红斑狼疮Systemic

Lupus

Erythematosus干燥综合症Sjogren's

Syndrome消化系统疾病肝硬化Liver

Cirrhosis克隆氏病Crohn's

Disease心血管系统疾病心肌梗死Myocardial

Infarction心肌缺血Myocardial

Ischemia动脉粥样硬化Atherosclerosis血液系统病再生障碍性贫血AplasticAnemia移植物抗宿主病GVHD白血病Leukemia呼吸系统疾病肺支气管发育不良Bronchopulmonary

Dysplasia肺气肿Emphysema慢性支气管炎Chronic

Bronchitis泌尿生殖系统疾病肾病Kidney

Transplant阳痿Erectile

Dysfunction运动系统疾病股骨头坏死Osteonecrosis

of

the

Femoral

Head骨关节炎Osteoarthritis皮肤病烧伤Burn内分泌系统疾病糖尿病Diabetes

Mellitus一、血液干细胞治疗缺血性血管病举例Critical

vascularischemiaisaglobalconcernwithlimitedtherapy

重度缺血性血管病是世界公认的难治性疾病Canstemcelltherapybeanefficacytherapyforcriticalvascularischemia?骨髓和血液中含有血管干细胞

FirsttherapyofcriticallimbischemiawithautologousbloodstemcellsMorethan5000patientshavebeentreatedbythistherapyBloodstemcellsLocalinjectionAngiogenicAndanti-inflammationRepairedTissueLimbIschemiaBloodreperfusionOnepatientwithadvancedcriticallimbischemia(CLI)receivedthistreatment.ChinJHematol,2003.HanZCetal.,DiabetesCare,2005Asignificantimprovementofdiabeticmicroangiopathywasobserved.Noobviousadverseeffectwasobservedaftercelltherapy.骨髓与外周血干细胞治疗下肢缺血的疗效比较研究M-PBMNCBMMNC76recruited74recruited72patientsweretreated132ischemiclimbs(ABI<0.9)wereinjectedwithBM-MNC2excluded1excluded2patientsdiscontinuedduetoamputation73patientsassessedforprimaryoutcomeat12week75patientsweretreated138ischemiclimbs(ABI<0.9)wereinjectedwithM-PBMNC3patientsdiscontinuedduetoamputation69patientsassessedforprimaryoutcomeat12weekHuangPP,HanZC.ThrombHaemost,2007临床试验结果表明两种疗法均安全有效、简单经济。外周血干细胞移植具有取材方便、可以多次使用等优点下肢缺血患者采用标准化移植方案接受外周血或骨髓干细胞移植的临床疗效分析（多中心合作）发现PB-MNC（治疗组76例）与骨髓单个核细胞（BM-MNC）移植（对照组74例）治疗下肢缺血均有效，两组总体临床疗效相比无显著性差异。但两组中糖尿病下肢缺血患者治疗后踝压指数（ABI）的增加值均显著性低于无糖尿病下肢缺血患者（治疗组p=0.037;对照组p=0.027在溃疡愈合率和截肢手术率方面也是非糖尿病下肢缺血患者要显著优于糖尿病下肢缺血患者。理论上可以治疗下肢缺血的细胞来源来源论文数病例数未截肢数避免截肢率外周血932236210894.27%脐带3676394.02%脐带血5322887.5%骨髓912211184183.27%脂肪111100%不同组织来源的干细胞治疗下肢缺血的病例数统计发表在中文科技刊物的临床研究结果(截至于2015.10.31)二、围产期干细胞的研究:

围产期干细胞库,细胞产品及其临床应用

Perinatalstemcells:primitivestemcellslocatedintheorgansoffetusesFetalproperstemcellscomefromthetissueofthefetusproper,andaregenerallyobtainedafteranabortion.Thesestemcellsarenotimmortalbuthaveahighlevelofdivisionandaremultipotent.Extraembryonicstemcellscomefromplacenta,umbilicalcord,amnioticfluidandmembranes.Thesestemcellsareacquiredafterbirth,andarenotimmortalbuthaveahighlevelofcelldivision,andarepluripotentormultipotent.Placentastemcellbanking

andmedicaltherapiesStemcelltherapiesTissueandorganengineeringandtherapiesStemcelldifferentiationandexpansionStemcellbankingPlacentastemcellbanking

andmedicaltherapiesPlacentastemcellbanking

andmedicaltherapiesStemcellbankingStemcelldifferentiationandexpansionStemcellbankingStemcelltherapiesStemcelldifferentiationandexpansionStemcellbankingTissueandorganengineeringandtherapiesStemcelltherapiesStemcelldifferentiationandexpansionStemcellbankingTissueandorganengineeringandtherapiesStemcelltherapiesTissueandorganengineeringandtherapiesStemcelldifferentiationandexpansionStemcelltherapiesTissueandorganengineeringandtherapiesStemcellbankingStemcelldifferentiationandexpansionStemcelltherapiesTissueandorganengineeringandtherapiesStemcellbankingStemcelldifferentiationandexpansionStemcelltherapiesTissueandorganengineeringandtherapiesStemcellbankingStemcelldifferentiationandexpansionStemcelltherapiesTissueandorganengineeringandtherapiesPlacentastemcellbanking

andmedicaltherapiesStemcellbankingStemcelldifferentiationandexpansionStemcelltherapiesTissueandorganengineeringandtherapiesPlacentastemcellbanking

andmedicaltherapiesStemcellbankingStemcelldifferentiationandexpansionStemcelltherapiesTissueandorganengineeringandtherapiesPlacentastemcellbanking

andmedicaltherapiesStemcellbankingStemcelldifferentiationandexpansionStemcelltherapiesTissueandorganengineeringandtherapies治疗用围产期组织干细胞库及其产品制备流程BullAcadNatlMed.2009;CellTransplant,2011;StemCellDev,2012;StemCellInt,2012Hanetal.Humanperinatalstemcellbanking:experiencesandperspectivesforregenerativemedicine.Science(suppl),2012Firstbankofperinatalmesenchymalstemcells

forclinicalusesestablishedin2005干细胞银行-干细胞库–干细胞药房2025/4/7干细胞制品的安全性研究干细胞治疗多种组织损伤的临床前动物实验Blooddisease: Haematologica,2006Vasculardisease: JCellBiochem,2007Heartdiseases: JCellBiochem,2009;AnnThoracSurg,2011Stroke: Transplantation,2009Cerebralhemorrhage:CellPhysiolBiochem.,2009Liverinjury:Cytotherapy,2009,2010MultipleSclerosis: MultScler.,2009Colitis: CellTransplant,2011Myastheniagravis: ScandJImmunol.2010Diabetes: JCellMolMed,2008；Diabetes，in

pressUveoretinitis: InvestOphthalmolVisSci.2011Acutelunginjury: CellPhysiolBiochem.,2011BeforecelltherapyaftercelltherapyPilotclinicaltrialofmesenchymalstemcells胎盘间充质干细胞治疗II型糖尿病MultScler.2009May;15(5):644-6（多发性硬化症）

Before

OnemonthlateScience(suppl),2012自体围产期干细胞共移植治疗重症再生障碍性贫血Theresultsobtainedfrom50patientstreatedindicatethatthisnewstrategyiseffectiveinimprovingdonorengraftmentandreducingsevereGVHD,whichwillprovideafeasibleoptionforthetherapyofhigh-riskhematologicmalignancy.造血干细胞与间充质干细胞共移植治疗难治性恶性血液病造血干细胞和间充质干细胞移植治疗重症再障DatasuggestthatUC-MSCs,possiblythankstotheirpotentimmunosuppressiveeffectonallo-reactivehostTlymphocytesescapingthepreparativeregimen,reducetheriskofgraftfailureandsevereGVHDinhaplo-HSCT.

成体干细胞共移植救治放射损伤新技术的建立与应用干细胞治疗心脏病的给药途径及模式WuKH,HanZC.AgeingResRev.2011国内外不同组织来源的细胞治疗心脏病的病例数统计来源病例数有效病例数有效率骨髓MNC36936498.6%外周血MNC8484100%脐带血MNC1079790.7%脐带MSC151493.3%发表在中英文科技刊物的临床研究结果(截至于2015.10.31)

干细胞凝胶外用治疗难治性皮肤炎症损伤1:359-72,2012.干细胞库（资源保存）