干細(xì)胞治療自身免疫性疾病課件

1、UB-MSC: the new gold standard to treat several human diseases, especially autoimmune diseasesInstitute of Clinical Medicine, Renmin Hospital, Hubei University of MedicineJunming Tang2015.82020/11/31UB-MSC: the new gold standard Outline一、Definition二、Characteristics三、Classification四、Pathogenesis五、Trad

2、itional therapy六、Biotherapy(antibody、vaccine、gene therapy ) 七、Cell therapy(DC、HSC、MSC)2020/11/32Outline一、Definition2020/11/32一、Definition Autoimmunity refer to the immune responses to self cells or self components.Autoimmune disease refer to the disease state resulted from immune responses directed

3、against self cells or self components. 2020/11/33一、Definition Autoimmunity refe二、Characteristics Autoimmune antibody and (or) autoreactive T lymphocyte can be detected.Autoimmune antibody and (or) autoreactive T lymphocyte mediate immune response which lead to damage or functional disturbanceThe tur

4、nover of pathogenetic condition relate with autoimmune response intensityRecurrent attacks and chronic 2020/11/34二、Characteristics Autoimmune a三、ClassificationOrgan-specific autoimmune disease Graves disease、insulin-dependent diabetes mellitusSystemic autoimmune disease systemic lupus erythematosus2

5、020/11/35三、ClassificationOrgan-specific四、PathogenesisAutoimmune antibodyDisfunction immunologic system(autoreactive T lymphocyte)Genetics and endocrine2020/11/36四、PathogenesisAutoimmune antibExamples of Human Autoimmune Diseases with Possible Molecular Mimicry as a Mechanism Clin Rev Allergy Immunol

6、. 2012; 42(1): 102C112020/11/37Examples of Human Autoimmune D類別病名自身抗原非器官特異性系統(tǒng)性紅斑狼瘡胞核成分（DNA,DNP,RNP,Sm）類風(fēng)濕性關(guān)節(jié)炎變性IgG,類風(fēng)濕相關(guān)的核抗原干燥綜合征細(xì)胞核（SS-A,SS-B）,唾液腺管胞漿線粒體,微粒體,紅細(xì)胞,血小板混合性結(jié)締組織病細(xì)胞核（RNP）器官特異性喬本甲狀腺炎甲狀腺球蛋白、微粒體Graves病甲狀腺細(xì)胞表面THS受體Addison病腎上腺皮質(zhì)細(xì)胞幼年型糖尿病胰島細(xì)胞萎縮性胃炎胃壁細(xì)胞潰瘍性結(jié)腸炎結(jié)腸上皮細(xì)胞原發(fā)性膽汁性肝硬化膽小管細(xì)胞、線粒體重癥肌無力乙酰膽堿受體自身免疫

7、性溶血性貧血紅細(xì)胞特發(fā)性血小板減少性紫癜血小板常見自身免疫病 2020/11/38類別病名自身抗原非器官特異性系統(tǒng)性紅斑狼瘡胞核成分（D五、Traditional therapyGeneral therapyCortisoneImmune inhibitorsOthers 2020/11/39五、Traditional therapyGeneral t六、BiotherapyAntibodyVaccinePharmaceutical Biotechnology 2012, 19( 4) : 364 368. ChineseJournalofNewDrugs2011, 20(8)2020/11/

8、310六、BiotherapyAntibodyPharmaceutHow to better solve the suffering of patientsNew ways2020/11/311How to better solve the suf七、Gene and Cell therapyDC、NK、CIK、B、T、LAKStem cells(HSC、MSC.）2020/11/312七、Gene and Cell therapyDC、NK、C八、Stem Cell therapy for AID1.Definition & Historic landmarks 2.Cell types:

9、MSC origin and 3.Cell harvest, culture and store4.Delivery method5.Comparative Evaluation6.Animal experimental7.Mechanism8. Clinical experimental 9.Conclusion2020/11/313八、Stem Cell therapy for AID1.D1.Stem cells2020/11/3141.Stem cells2020/11/31415Historic landmarks in the field of stem cell biologyC

10、irc Res. 2014;114:21-27.)2020/11/31515Historic landmarks in the fi2.Cell types162020/11/3162.Cell types162020/11/316MSC: origin and biological traitsCsar Nombela-Arrieta,Nature Reviews Molecular Cell Biology 12, 126-131 (2011)SynoviumCartilageDental pulpBone marrow Kidney Pancreas Adipose tissue Mus

11、cle Brain liverTonsilPlacentaUmbilical CordThymusPericytesAmniotic fluid2020/11/317MSC: origin and biological tra3.Isolation, culture store of mesenchymal stem cells from Whartons jelly J. Biomedical Science and Engineering, 2012, 5, 580-586 Cryobiology. 2014 Jun;68(3):467-72. Current Stem Cell Rese

12、arch & Therapy, 2013, 8, 144-1552020/11/3183.Isolation, culture store of4.Delivery methodsPMID: 260680302020/11/3194.Delivery methodsPMID: 2606805.Comparative Evaluation of different MSCsJ Immunol Res. 2015:394917. 2020/11/3205.Comparative Evaluation of diThe advantages of UB-MSCsStem Cells Internat

13、ional, 2013,2461342020/11/321The advantages of UB-MSCsStem Table 1: Phenotypic pro WJ-MSCs compared to MSCs from other sources2020/11/322Table 1: Phenotypic pro WJ-MSCTable 2: Transcriptomic pro WJ-MSCs compared to MSCs from other sources2020/11/323Table 2: Transcriptomic pro WJTable 2: Transcriptom

14、ic pro WJ-MSCs compared to MSCs from other sources2020/11/324Table 2: Transcriptomic pro WJThe differentiation advantages of WJ-MSCs compared to MSCs from other sourcesTissue Eng Part B Rev. 2014 Oct;20(5):523-44. 2020/11/325The differentiation advantagesBetter: autologous/allogenic?Allogenic health

15、y BM-MSC, UB-MSCCellular Immunology 293 (2015) 1131212020/11/326Better: autologous/allogenic?ASummary . 1.Umbilical cord derived MSCs are more primitive, proliferative, regenerative, homing and immuno-suppressive than their adult counterparts2.Healthy UB-MSC is better than MSC from patient-self2020/

16、11/327Summary . 1.Umbilical cord der6.Preclinical Efficacy and Mechanisms of Mesenchymal Stem Cells in Animal Models of Autoimmune DiseasesImmune Network 2014;14(2):81-882020/11/3286.Preclinical Efficacy and Mec7.Mesenchymal stem cell immunosuppression of innate/adaptive immune cellsWorld J Stem Cel

17、ls 2014; 6(5): 526-5392020/11/3297.Mesenchymal stem cell immunoDifferential toll-like receptor stimulation affects mesenchymal stem cell immune-modulation 2020/11/330Differential toll-like receptoSummaryImmunosuppression2020/11/331SummaryImmunosuppression2020/1Permit for application of UB-MSC in hum

18、an AIDCellStemCell 17,July2,20152020/11/332Permit for application of UB-8.Clinical trails: Stem cell for AID2020/11/3338.Clinical trails: Stem cell fClinical trials (registered as of Aug.8 2015 ) using HSChaematologica | 2010; 95(2):184-193.2020/11/334Clinical trials (registered asClinical trials (r

19、egistered ) using MSC During HSC transplantationMaria Ester Bernardo, Immunology Letters,Available online 25 June 2015Experimental & Molecular Medicine (2013) 45, e22020/11/335Clinical trials (registered ) Clinical trials (registered as of Aug.8 2015 ) using MSCCellStemCell 17,July2,2015Annu. Rev. I

20、mmunol. 2013. 31:2853162020/11/336Clinical trials (registered asClinical trials (registered as of Aug.8 2015 ) using UB-MSC for AID2020/11/337Clinical trials (registered asSafety and feasibilityWoodworthand Furst Arthritis Research&Therapy 2014, 16:1132020/11/338Safety and feasibilityWoodwortRisks a

21、nd Rewards Stem Cells Dev 2015 Jun.PMID: 260680302020/11/339Risks and Rewards Stem Cells DEffects: CausesEg: Mesenchymal stem cells can induce neuron recovery in multiple sclerosisAmerican Journal of Occupational Therapy, 2014,68, 2732.Cellular Immunology 293 (2015) 113121Stem Cell Rev. 2012;8(3):94

22、0-52.2020/11/340Effects: CausesEg: MesenchymaSummary: FDA permit for UB-MSC多系統(tǒng)硬化風(fēng)濕性關(guān)節(jié)炎I型糖尿病系統(tǒng)性紅斑狼瘡狼瘡腎炎肝夏科氏肝硬變自身免疫性肝炎IgA腎病克隆病色素性視網(wǎng)膜炎血栓閉塞性脈管炎進(jìn)行性面部偏側(cè)萎縮2020/11/341Summary: FDA permit for UB-MSCTake-home messagesUB-MSC: the new gold standard to treat several human diseases, especially autoimmune and neur

23、odegenerative diseases2020/11/342Take-home messagesUB-MSC: the 1 Tang JM, Luo B, Xiao JH, Lv YX, Li XL, Zhao JH, Zheng F, Zhang L, Chen L, Yang JY, Guo LY, Wang L, Yan YW, Pan YM, Wang JN, Li DS, Wan Y, Chen SY. VEGF-A promotes cardiac stem cell engraftment and myocardial repair in the infarcted hea

24、rt.Int J Cardiol. 2015;183:221-31.2. Xie WB, Li Z, Shi N, Guo X, Tang J, Ju W, Han J, Liu T, Bottinger EP, Chai Y, Jose PA, Chen SY.Smad2 and myocardin-related transcription factor B cooperatively regulate vascular smooth muscle differentiation from neural crest cells.Circ Res. 2013;113(8):e76-86. 3

25、. Tang JM, Wang JN, Zhang L, Zheng F, Yang JY, Kong X, Guo LY, Chen L, Huang YZ, Wan Y, Chen SY.VEGF/SDF-1 promotes cardiac stem cell mobilization and myocardial repair in the infarcted heart.Cardiovasc Res. 2011; 91(3):402-11. 4. Tang J, Wang J, Yang J, Kong X, Zheng F, Guo L, Zhang L, Huang Y. Mes

26、enchymal stem cells over-expressing SDF-1 promote angiogenesis and improve heart function in experimental myocardial infarction in rats. Eur J Cardiothorac Surg. 2009, 36(4):644-50. PMID: 19524448.5.Tang J, Xie Q, Pan G, Wang J, Wang M. Mesenchymal stem cells participate in angiogenesis and improve

27、heart function in rat model of myocardial ischemia with reperfusion. Eur J Cardiothorac Surg. 2006; 30(2):353-61.6.Tang J, Wang J, Zheng F, Yang J, Kong X, Guo L, Zhang L, Huang Y. Vascular endothelial growth factor promotes cardiac stem cell migration via the PI3K/Akt pathway. Experimental Cell Res

28、earch.2009, 315(20):3521-3531. 7. Tang J, Wang J, Kong X, Zheng F, Yang J, Guo L, Zhang L, Huang Y. Mesenchymal stem cells modified with stromal cell-derived factor 1 improve remodeling via paracrine activation of hepatocyte growth factor in a rat model of myocardial infarction. Moleculars and Cells

29、. 2010,29(1):1-10.8.Tang J, Wang J, Kong X, Yang J, Zheng F, Guo L, Zhang L, Huang Y. Adenovirus-mediated stromal cell-derived- factor-1 alpha gene transfer improves cardiac structure and function after experimental myocardial infarction through angiogenic and antifibrotic actions. Molecular Biology

30、 Reports. Mol Biol Rep. 2010; 37(4):1957-69.9. Tang J, Wang J, Zheng F, Kong X, Guo L, Yang J, Zhang L, Huang Y.Combination of chemokine and angiogenic factor genes and mesenchymal stem cells could enhance angiogenesis and improve cardiac function after acute myocardial infarction in rats. Mol Cell

31、Biochem. 2010; 339(1-2):107-18.10. Tang JM, Yuan J, Li Q, Wang JN, Kong X, Zheng F, Zhang L, Chen L, Guo LY, Huang YH, Yang JY, Chen SY.Acetylcholine induces mesenchymal stem cell migration via Ca2+ /PKC/ERK1/2 signal pathway.J Cell Biochem. 2012;113(8):2704-13.11. Zhang L, Dong XW, Wang JN, Tang JM

32、, Yang JY, Guo LY, Zheng F, Kong X, Huang YZ, Chen SY.PEP-1-CAT-transduced mesenchymal stem cells acquire an enhanced viability and promote ischemia-induced angiogenesis.PLoS One. 2012;7(12):e52537Publication 2020/11/3431 Tang JM, Luo B, Xiao JH, LPublication 6.Tang J, Wang J, Zheng F, Yang J, Kong

33、X, Guo L, Zhang L, Huang Y. Vascular endothelial growth factor promotes cardiac stem cell migration via the PI3K/Akt pathway. Experimental Cell Research.2009, 315(20):3521-3531. 7. Tang J, Wang J, Kong X, Zheng F, Yang J, Guo L, Zhang L, Huang Y. Mesenchymal stem cells modified with stromal cell-derived factor 1 improve remodeling via paracrine activation of hepatocyte growth factor in a rat model of myocardial infarction. Moleculars and Cells. 2010,29(1):1-10.8.Tang J, Wang J, Ko