干细胞治疗自身免疫性疾病课件.ppt

UB-MSC: the new gold standard to treat several human diseases, especially autoimmune diseases,Institute of Clinical Medicine, Renmin Hospital, Hubei University of Medicine,Junming Tang2015.8,2020/11/3,1,UB-MSC: the new gold standard,Outline,一、Definition二、Characteristics三、Classification四、Pathogenesis五、Traditional therapy六、Biotherapy(antibody、vaccine、gene therapy ) 七、Cell therapy(DC、HSC、MSC),2020/11/3,2,Outline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 against self cells or self components.,2020/11/3,3,一、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 turnover of pathogenetic condition relate with autoimmune response intensityRecurrent attacks and chronic,2020/11/3,4,二、Characteristics Autoimmune a,三、Classification,Organ-specific autoimmune disease Graves disease、insulin-dependent diabetes mellitusSystemic autoimmune disease systemic lupus erythematosus,2020/11/3,5,三、ClassificationOrgan-specific,四、Pathogenesis,Autoimmune antibodyDisfunction immunologic system(autoreactive T lymphocyte)Genetics and endocrine,2020/11/3,6,四、PathogenesisAutoimmune antib,Examples of Human Autoimmune Diseases with Possible Molecular Mimicry as a Mechanism,Clin Rev Allergy Immunol. 2012; 42(1): 102C11,2020/11/3,7,Examples of Human Autoimmune D,常见自身免疫病,2020/11/3,8,类别病名自身抗原非器官特异性系统性红斑狼疮胞核成分（D,五、Traditional therapy,General therapyCortisoneImmune inhibitorsOthers,2020/11/3,9,五、Traditional therapyGeneral t,六、Biotherapy,AntibodyVaccine,Pharmaceutical Biotechnology 2012, 19( 4) : 364 368. ChineseJournalofNewDrugs2011, 20(8),2020/11/3,10,六、BiotherapyAntibodyPharmaceut,How to better solve the suffering of patients,New ways,2020/11/3,11,How to better solve the suf,七、Gene and Cell therapy,DC、NK、CIK、B、T、LAKStem cells(HSC、MSC.）,2020/11/3,12,七、Gene and Cell therapyDC、NK、C,八、Stem Cell therapy for AID,1.Definition & Historic landmarks 2.Cell types: MSC origin and 3.Cell harvest, culture and store4.Delivery method5.Comparative Evaluation6.Animal experimental7.Mechanism8. Clinical experimental 9.Conclusion,2020/11/3,13,八、Stem Cell therapy for AID1.D,1.Stem cells,2020/11/3,14,1.Stem cells2020/11/314,15,Historic landmarks in the field of stem cell biology,Circ Res. 2014;114:21-27.),2020/11/3,15,15Historic landmarks in the fi,2.Cell types,16,2020/11/3,16,2.Cell types162020/11/316,MSC: origin and biological traits,Csar Nombela-Arrieta,Nature Reviews Molecular Cell Biology 12, 126-131 (2011),Synovium,Cartilage,Dental pulp,Bone marrow,Kidney,Pancreas,Adipose tissue,Muscle,Brain,liver,Tonsil,Placenta,Umbilical Cord,Thymus,Pericytes,Amniotic fluid,2020/11/3,17,MSC: origin and biological tra,3.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 Research & Therapy, 2013, 8, 144-155,2020/11/3,18,3.Isolation, culture store of,4.Delivery methods,PMID: 26068030,2020/11/3,19,4.Delivery methodsPMID: 260680,5.Comparative Evaluation of different MSCs,J Immunol Res. 2015:394917.,2020/11/3,20,5.Comparative Evaluation of di,The advantages of UB-MSCs,Stem Cells International, 2013,246134,2020/11/3,21,The advantages of UB-MSCsStem,Table 1: Phenotypic pro WJ-MSCs compared to MSCs from other sources,2020/11/3,22,Table 1: Phenotypic pro WJ-MSC,Table 2: Transcriptomic pro WJ-MSCs compared to MSCs from other sources,2020/11/3,23,Table 2: Transcriptomic pro WJ,Table 2: Transcriptomic pro WJ-MSCs compared to MSCs from other sources,2020/11/3,24,Table 2: Transcriptomic pro WJ,The differentiation advantages of WJ-MSCs compared to MSCs from other sources,Tissue Eng Part B Rev. 2014 Oct;20(5):523-44.,2020/11/3,25,The differentiation advantages,Better: autologous/allogenic?,Allogenic healthy BM-MSC, UB-MSC,Cellular Immunology 293 (2015) 113121,2020/11/3,26,Better: autologous/allogenic?A,Summary,.,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-self,2020/11/3,27,Summary . 1.Umbilical cord der,6.Preclinical Efficacy and Mechanisms of Mesenchymal Stem Cells in Animal Models of Autoimmune Diseases,Immune Network 2014;14(2):81-88,2020/11/3,28,6.Preclinical Efficacy and Mec,7.Mesenchymal stem cell immunosuppression of innate/adaptive immune cells,World J Stem Cells 2014; 6(5): 526-539,2020/11/3,29,7.Mesenchymal stem cell immuno,Differential toll-like receptor stimulation affects mesenchymal stem cell immune-modulation,2020/11/3,30,Differential toll-like recepto,Summary,Immunosuppression,2020/11/3,31,SummaryImmunosuppression2020/1,Permit for application of UB-MSC in human AID,CellStemCell 17,July2,2015,2020/11/3,32,Permit for application of UB-,8.Clinical trails: Stem cell for AID,2020/11/3,33,8.Clinical trails: Stem cell f,Clinical trials (registered as of Aug.8 2015 ) using HSC,haematologica | 2010; 95(2):184-193.,2020/11/3,34,Clinical trials (registered as,Clinical trials (registered ) using MSC During HSC transplantation,Maria Ester Bernardo, Immunology Letters,Available online 25 June 2015,Experimental & Molecular Medicine (2013) 45, e2,2020/11/3,35,Clinical trials (registered ),Clinical trials (registered as of Aug.8 2015 ) using MSC,CellStemCell 17,July2,2015,Annu. Rev. Immunol. 2013. 31:285316,2020/11/3,36,Clinical trials (registered as,Clinical trials (registered as of Aug.8 2015 ) using UB-MSC for AID,2020/11/3,37,Clinical trials (registered as,Safety and feasibility,Woodworthand Furst Arthritis Research&Therapy 2014, 16:113,2020/11/3,38,Safety and feasibilityWoodwort,Risks and Rewards,Stem Cells Dev 2015 Jun.PMID: 26068030,2020/11/3,39,Risks and Rewards Stem Cells D,Effects: CausesEg: Mesenchymal stem cells can induce neuron recovery in multiple sclerosis,American Journal of Occupational Therapy, 2014,68, 2732.,Cellular Immunology 293 (2015) 113121,Stem Cell Rev. 2012;8(3):940-52.,2020/11/3,40,Effects: CausesEg: Mesenchyma,Summary: FDA permit for UB-MSC,多系统硬化,风湿性关节炎,I型糖尿病,系统性红斑狼疮,狼疮肾炎,肝夏科氏肝硬变,自身免疫性肝炎,IgA肾病,克隆病,色素性视网膜炎,血栓闭塞性脉管炎,进行性面部偏侧萎缩,2020/11/3,41,Summary: FDA permit for UB-MSC,Take-home messages,UB-MSC: the new gold standard to treat several human diseases, especially autoimmune and neurodegenerative diseases,2020/11/3,42,Take-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 heart.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. 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. Mesenchymal 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 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 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, 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 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 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, 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):e52537,Publication,2020/11/3,43,1 Tang JM, Luo B, Xiao JH, L,Publication,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 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, 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 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 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, 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):e52537,2020/11/3,44,Publication 6.Tang J, Wang J,2020/11/3,45,2020/11/345,