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美國《科學》雜志七次評出干細胞為21世紀,干細胞再生醫學有希望形成巨大的健康產業美總統第13505號行政令-干細胞科研的解禁令備忘錄(2009年3月11日)十大科學成果之一又一場醫療革命2015年,習近平總書記指出,“兩彈一星”、多復變函數論、陸相成油理論、人工合成牛胰島素等成就,高溫超導、中微子物理、量子反常霍爾效應、納米科技、干細胞研究、人類基因組測序等基礎科學突破,為我國作為一個有世界影響的大國奠定了重要基礎。2009年,溫家寶總理指出:干細胞研究促進了再生醫學的發展,這是繼藥物治療、手術治療之后的又一場醫療革命,我們要力爭在干細胞研究的更多領域取得領先地位。
巨大的社會和經濟效益預計干細胞市場在2025可達$4000億元。Onecell,OnedreamStemcellSelf-renewDifferentiationFormtissues&organsIndividualdevelopmentmaturationandageingDifferentiationWhatarestemcells?
什么是干細胞?Stemcells:unitsofdevelopment,unitsofregeneration,andunitsinevolution.WeissmanIL.Cell.100:157–68,2000.
干細胞:機體發育、再生和進化的單元DifferentiationPotencydefinitionofstemcells–干細胞分類Totipotent(全能)
stemcellscandifferentiateintoembryonicandextraembryoniccelltypes.Pluripotent(亞全能)stemcellsarethedescendantsoftotipotentcellsandcandifferentiateintonearlyallcells,i.e.cellsderivedfromanyofthethreegermlayer.Multipotent(多能)
stemcellscandifferentiateintoanumberofcelltypes,butonlythoseofacloselyrelatedfamilyofcells.Oligopotent
(寡能)stemcellscandifferentiateintoonlyafewcelltypes,suchaslymphoidormyeloidstemcells.]Unipotent(單能)
stemcellscanproduceonlyonecelltype,theirown,buthavethepropertyofself-renewal,whichdistinguishesthemfromnon-stemcellsInducedpluripotentstemcells–誘導多能干細胞間充質干細胞(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–干細胞臨床用途
內在因素環境因素DNA損傷腫瘤與干細胞干細胞衰老腫瘤組織衰老全身衰老機能衰老Relationamongstemcells,agingandcancer干細胞與衰老和腫瘤的關系免疫細胞治療是21世紀最前沿的腫瘤治療方法腫瘤自體細胞免疫療法適用于多種腫瘤,包括惡性黑色素瘤、前列腺癌、腎癌、膀胱癌、卵巢癌、結腸癌、直腸癌、乳腺癌、宮頸癌、肺癌、喉癌、鼻咽癌、胰腺癌、肝癌、胃癌等.實體瘤手術后防止復發,也可以用于多發性骨髓瘤、B淋巴瘤和白血病等血液系統惡性腫瘤的復發CAR-T:醫藥界的阿波羅11號
0-1010-20 20-30 30-4040-5050-60>60AGEINYEARSTOTALSTEMCELLS(LOGSCALE)THENUMBEROFSTEMCELLSDECREASESBYALOGFOREVERYDECADEOFLIFEAgingandstemcelllossandsenescenceThehallmarksofAging衰老的特征Cell,2013中國干細胞治療技術研究發展歷程Before19901991-20002001-20052006-20102011-2015骨髓造血干細胞血液造血干細胞骨髓MSC胎盤臍帶MSC脂肪干細胞血管干細胞其它組織干細胞胚胎干細胞誘導多能干細胞研究熱點研究點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-干細胞臨床應用神經系統疾病脊髓損傷SpinalCordInjury腦卒中Stroke腦癱CerebralPalsy肌萎縮側索硬化AmyotrophicLateralSclerosis帕金森病Parkinson’sDisease多發性硬化MultipleSclerosis老年性癡呆Alzheimer's
Disease免疫系統疾病系統性硬化Systemic
Sclerosis系統性紅斑狼瘡Systemic
Lupus
Erythematosus干燥綜合癥Sjogren's
Syndrome消化系統疾病肝硬化Liver
Cirrhosis克隆氏病Crohn's
Disease心血管系統疾病心肌梗死Myocardial
Infarction心肌缺血Myocardial
Ischemia動脈粥樣硬化Atherosclerosis血液系統病再生障礙性貧血AplasticAnemia移植物抗宿主病GVHD白血病Leukemia呼吸系統疾病肺支氣管發育不良Bronchopulmonary
Dysplasia肺氣腫Emphysema慢性支氣管炎Chronic
Bronchitis泌尿生殖系統疾病腎病Kidney
Transplant陽痿Erectile
Dysfunction運動系統疾病股骨頭壞死Osteonecrosis
of
the
Femoral
Head骨關節炎Osteoarthritis皮膚病燒傷Burn內分泌系統疾病糖尿病Diabetes
Mellitus一、血液干細胞治療缺血性血管病舉例Critical
vascularischemiaisaglobalconcernwithlimitedtherapy
重度缺血性血管病是世界公認的難治性疾病Canstemcelltherapybeanefficacytherapyforcriticalvascularischemia?骨髓和血液中含有血管干細胞
FirsttherapyofcriticallimbischemiawithautologousbloodstemcellsMorethan5000patientshavebeentreatedbythistherapyBloodstemcellsLocalinjectionAngiogenicAndanti-inflammationRepairedTissueLimbIschemiaBloodreperfusionOnepatientwithadvancedcriticallimbischemia(CLI)receivedthistreatment.ChinJHematol,2003.HanZCetal.,DiabetesCare,2005Asignificantimprovementofdiabeticmicroangiopathywasobserved.Noobviousadverseeffectwasobservedaftercelltherapy.骨髓與外周血干細胞治療下肢缺血的療效比較研究M-PBMNCBMMNC76recruited74recruited72patientsweretreated132ischemiclimbs(ABI<0.9)wereinjectedwithBM-MNC2excluded1excluded2patientsdiscontinuedduetoamputation73patientsassessedforprimaryoutcomeat12week75patientsweretreated138ischemiclimbs(ABI<0.9)wereinjectedwithM-PBMNC3patientsdiscontinuedduetoamputation69patientsassessedforprimaryoutcomeat12weekHuangPP,HanZC.ThrombHaemost,2007臨床試驗結果表明兩種療法均安全有效、簡單經濟。外周血干細胞移植具有取材方便、可以多次使用等優點下肢缺血患者采用標準化移植方案接受外周血或骨髓干細胞移植的臨床療效分析(多中心合作)發現PB-MNC(治療組76例)與骨髓單個核細胞(BM-MNC)移植(對照組74例)治療下肢缺血均有效,兩組總體臨床療效相比無顯著性差異。但兩組中糖尿病下肢缺血患者治療后踝壓指數(ABI)的增加值均顯著性低于無糖尿病下肢缺血患者(治療組p=0.037;對照組p=0.027在潰瘍愈合率和截肢手術率方面也是非糖尿病下肢缺血患者要顯著優于糖尿病下肢缺血患者。理論上可以治療下肢缺血的細胞來源來源論文數病例數未截肢數避免截肢率外周血932236210894.27%臍帶3676394.02%臍帶血5322887.5%骨髓912211184183.27%脂肪111100%不同組織來源的干細胞治療下肢缺血的病例數統計發表在中文科技刊物的臨床研究結果(截至于2015.10.31)二、圍產期干細胞的研究:
圍產期干細胞庫,細胞產品及其臨床應用
Perinatalstemcells:primitivestemcellslocatedintheorgansoffetusesFetalproperstemcellscomefromthetissueofthefetusproper,andaregenerallyobtainedafteranabortion.Thesestemcellsarenotimmortalbuthaveahighlevelofdivisionandaremultipotent.Extraembryonicstemcellscomefromplacenta,umbilicalcord,amnioticfluidandmembranes.Thesestemcellsareacquiredafterbirth,andarenotimmortalbuthaveahighlevelofcelldivision,andarepluripotentormultipotent.Placentastemcellbanking
andmedicaltherapiesStemcelltherapiesTissueandorganengineeringandtherapiesStemcelldifferentiationandexpansionStemcellbankingPlacentastemcellbanking
andmedicaltherapiesPlacentastemcellbanking
andmedicaltherapiesStemcellbankingStemcelldifferentiationandexpansionStemcellbankingStemcelltherapiesStemcelldifferentiationandexpansionStemcellbankingTissueandorganengineeringandtherapiesStemcelltherapiesStemcelldifferentiationandexpansionStemcellbankingTissueandorganengineeringandtherapiesStemcelltherapiesTissueandorganengineeringandtherapiesStemcelldifferentiationandexpansionStemcelltherapiesTissueandorganengineeringandtherapiesStemcellbankingStemcelldifferentiationandexpansionStemcelltherapiesTissueandorganengineeringandtherapiesStemcellbankingStemcelldifferentiationandexpansionStemcelltherapiesTissueandorganengineeringandtherapiesStemcellbankingStemcelldifferentiationandexpansionStemcelltherapiesTissueandorganengineeringandtherapiesPlacentastemcellbanking
andmedicaltherapiesStemcellbankingStemcelldifferentiationandexpansionStemcelltherapiesTissueandorganengineeringandtherapiesPlacentastemcellbanking
andmedicaltherapiesStemcellbankingStemcelldifferentiationandexpansionStemcelltherapiesTissueandorganengineeringandtherapiesPlacentastemcellbanking
andmedicaltherapiesStemcellbankingStemcelldifferentiationandexpansionStemcelltherapiesTissueandorganengineeringandtherapies治療用圍產期組織干細胞庫及其產品制備流程BullAcadNatlMed.2009;CellTransplant,2011;StemCellDev,2012;StemCellInt,2012Hanetal.Humanperinatalstemcellbanking:experiencesandperspectivesforregenerativemedicine.Science(suppl),2012Firstbankofperinatalmesenchymalstemcells
forclinicalusesestablishedin2005干細胞銀行-干細胞庫–干細胞藥房2025/4/7干細胞制品的安全性研究干細胞治療多種組織損傷的臨床前動物實驗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胎盤間充質干細胞治療II型糖尿病MultScler.2009May;15(5):644-6(多發性硬化癥)
Before
OnemonthlateScience(suppl),2012自體圍產期干細胞共移植治療重癥再生障礙性貧血Theresultsobtainedfrom50patientstreatedindicatethatthisnewstrategyiseffectiveinimprovingdonorengraftmentandreducingsevereGVHD,whichwillprovideafeasibleoptionforthetherapyofhigh-riskhematologicmalignancy.造血干細胞與間充質干細胞共移植治療難治性惡性血液病造血干細胞和間充質干細胞移植治療重癥再障DatasuggestthatUC-MSCs,possiblythankstotheirpotentimmunosuppressiveeffectonallo-reactivehostTlymphocytesescapingthepreparativeregimen,reducetheriskofgraftfailureandsevereGVHDinhaplo-HSCT.
成體干細胞共移植救治放射損傷新技術的建立與應用干細胞治療心臟病的給藥途徑及模式WuKH,HanZC.AgeingResRev.2011國內外不同組織來源的細胞治療心臟病的病例數統計來源病例數有效病例數有效率骨髓MNC36936498.6%外周血MNC8484100%臍帶血MNC1079790.7%臍帶MSC151493.3%發表在中英文科技刊物的臨床研究結果(截至于2015.10.31)
干細胞凝膠外用治療難治性皮膚炎癥損傷1:359-72,2012.干細胞庫(資源保存)
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