诱导多能干细胞在心血管疾病中的应用:效率及安全性
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摘要
背景:诱导多能干细胞是具有与胚胎干细胞相似特征的一类重编程细胞,能够定向分化成与患者特异性疾病相关表型的细胞,并且其临床应用避免了伦理道德问题。目的:综述诱导多能干细胞在心肌再生与修复、心血管疾病模型、药物研发与筛选、药物心脏毒性检测等应用中的研究进展。方法:检索PubMed数据库2006至2018年期间的相关文章,检索词为"induction of pluripotent stem cells,myocardial infarction,arrhythmia,cardiovascular disease,heart failure,heart transplantation,disease models,drugtoxicity",同时检索中国知网数据库2013至2018年期间的相关文章,检索词为"诱导多能干细胞,心血管疾病,心肌梗死,心律失常,心力衰竭,疾病模型,药物毒性"。对资料进行逐一初审,并查看每篇文献后的引文。结果与结论:诱导多能干细胞在心肌再生与修复、心血管疾病模型的建立、新药研发与筛选、药物心脏毒性检测等方面具有巨大的潜在应用价值,应用前景广阔,但是大部分研究尚处于实验研究阶段;另外其诱导效率低、存在致瘤性的安全问题将限制诱导多能干细胞的临床应用。
BACKGROUND: Induced pluripotent stem cells are a type of reprogrammed cells with similar characteristics to embryonic stem cells, which are capable of differentiating into phenotypes associated with patient specific diseases. Moreover, their clinical application avoids ethical issues. OBJECTIVE: To review the research progress of induced pluripotent stem cells in myocardial regeneration and repair, cardiovascular disease models, drug development and screening, and drug toxicity testing. METHODS: PubMed(2006-2018) and CNKI(2013-2018) databases were retrieved for relevant articles using the keywords of "induction of pluripotent stem cells; myocardial infarction; arrhythmia; cardiovascular disease; heart failure; heart transplantation; disease model; drug toxicity" in English and Chinese, respectively. The data were reviewed one by one, and the citations involved in the literatures were also reviewed. RESULTS AND CONCLUSION: Induced pluripotent stem cells have great potential value in myocardial regeneration and repair, establishment of cardiovascular disease models, new drug development and screening, and drug toxicity detection. The application prospect of the cells is broad, but most of the research is still in the experimental stage. In addition, safety problems, such as low induction efficiency and tumorigenicity, will limit the clinical application of induced pluripotent stem cells.
BACKGROUND: Induced pluripotent stem cells are a type of reprogrammed cells with similar characteristics to embryonic stem cells, which are capable of differentiating into phenotypes associated with patient specific diseases. Moreover, their clinical application avoids ethical issues. OBJECTIVE: To review the research progress of induced pluripotent stem cells in myocardial regeneration and repair, cardiovascular disease models, drug development and screening, and drug toxicity testing. METHODS: PubMed(2006-2018) and CNKI(2013-2018) databases were retrieved for relevant articles using the keywords of "induction of pluripotent stem cells; myocardial infarction; arrhythmia; cardiovascular disease; heart failure; heart transplantation; disease model; drug toxicity" in English and Chinese, respectively. The data were reviewed one by one, and the citations involved in the literatures were also reviewed. RESULTS AND CONCLUSION: Induced pluripotent stem cells have great potential value in myocardial regeneration and repair, establishment of cardiovascular disease models, new drug development and screening, and drug toxicity detection. The application prospect of the cells is broad, but most of the research is still in the experimental stage. In addition, safety problems, such as low induction efficiency and tumorigenicity, will limit the clinical application of induced pluripotent stem cells.
引文
[1]Mozaffarian D,Benjamin EJ,Go AS,et al.Heart disease and stroke statistics--2015 update:a report from the American Heart Association.Circulation.2015;131(4):e29-322.
[2]Go AS,Mozaffarian D,Roger VL,et al.Heart disease and stroke statistics--2013 update:a report from the American Heart Association.Circulation.2013;127(1):e6-e245.
[3]GBD 2013 Risk Factors Collaborators,Forouzanfar MH,Alexander L,et al.Global,regional,and national comparative risk assessment of 79 behavioural,environmental and occupational,and metabolic risks or clusters of risks in 188countries,1990-2013:a systematic analysis for the Global Burden of Disease Study 2013.Lancet.2015;386(10010):2287-2323.
[4]Chen CH,Sereti KI,Wu BM,et al.Translational aspects of cardiac cell therapy.J Cell Mol Med.2015;19(8):1757-1772.
[5]Pagidipati NJ,Gaziano TA.Estimating deaths from cardiovascular disease:a review of global methodologies of mortality measurement.Circulation.2013;127(6):749-756.
[6]Bergmann O,Bhardwaj RD,Bernard S,et al.Evidence for cardiomyocyte renewal in humans.Science.2009;324(5923):98-102.
[7]Lalit PA,Hei DJ,Raval AN,et al.Induced pluripotent stem cells for post-myocardial infarction repair:remarkable opportunities and challenges.Circ Res.2014;114(8):1328-1345.
[8]Okano H,Nakamura M,Yoshida K,et al.Steps toward safe cell therapy using induced pluripotent stem cells.Circ Res.2013;112(3):523-533.
[9]Takahashi K,Tanabe K,Ohnuki M,et al.Induction of pluripotent stem cells from adult human fibroblasts by defined factors.Cell.2007;131(5):861-872.
[10]Takahashi K,Yamanaka S.Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.Cell.2006;126(4):663-676.
[11]Okita K,Ichisaka T,Yamanaka S.Generation of germlinecompetent induced pluripotent stem cells.Nature.2007;448(7151):313-317.
[12]Yu T,Miyagawa S,Miki K,et al.In vivo differentiation of induced pluripotent stem cell-derived cardiomyocytes.Circ J.2013;77(5):1297-1306.
[13]Mandai M,Watanabe A,Kurimoto Y,et al.Autologous Induced Stem-Cell-Derived Retinal Cells for Macular Degeneration.N Engl J Med.2017;376(11):1038-1046.
[14]Sayed N,Liu C,Wu JC.Translation of Human-Induced Pluripotent Stem Cells:From Clinical Trial in a Dish to Precision Medicine.J Am Coll Cardiol.2016;67(18):2161-2176.
[15]Nam YJ,Song K,Luo X,et al.Reprogramming of human fibroblasts toward a cardiac fate.Proc Natl Acad Sci U S A.2013;110(14):5588-5593.
[16]Qian L,Huang Y,Spencer CI,et al.In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes.Nature.2012;485(7400):593-598.
[17]DidiéM,Christalla P,Rubart M,et al.Parthenogenetic stem cells for tissue-engineered heart repair.J Clin Invest.2013;123(3):1285-1298.
[18]Riegler J,Tiburcy M,Ebert A,et al.Human Engineered Heart Muscles Engraft and Survive Long Term in a Rodent Myocardial Infarction Model.Circ Res.2015;117(8):720-730.
[19]Ong SG,Huber BC,Lee WH,et al.Microfluidic Single-Cell Analysis of Transplanted Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes After Acute Myocardial Infarction.Circulation.2015;132(8):762-771.
[20]Chong JJ,Yang X,Don CW,et al.Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts.Nature.2014;510(7504):273-277.
[21]Kawamura M,Miyagawa S,Fukushima S,et al.Enhanced survival of transplanted human induced pluripotent stem cell-derived cardiomyocytes by the combination of cell sheets with the pedicled omental flap technique in a porcine heart.Circulation.2013;128(11 Suppl 1):S87-94.
[22]Ye L,Chang YH,Xiong Q,et al.Cardiac repair in a porcine model of acute myocardial infarction with human induced pluripotent stem cell-derived cardiovascular cells.Cell Stem Cell.2014;15(6):750-761.
[23]Shiba Y,Gomibuchi T,Seto T,et al.Allogeneic transplantation of iPS cell-derived cardiomyocytes regenerates primate hearts.Nature.2016;538(7625):388-391.
[24]Lan F,Lee AS,Liang P,et al.Abnormal calcium handling properties underlie familial hypertrophic cardiomyopathy pathology in patient-specific induced pluripotent stem cells.Cell Stem Cell.2013;12(1):101-113.
[25]Wu H,Lee J,Vincent LG,et al.Epigenetic Regulation of Phosphodiesterases 2A and 3A Underlies Compromisedβ-Adrenergic Signaling in an iPSC Model of Dilated Cardiomyopathy.Cell Stem Cell.2015;17(1):89-100.
[26]Liang P,Lan F,Lee AS,et al.Drug screening using a library of human induced pluripotent stem cell-derived cardiomyocytes reveals disease-specific patterns of cardiotoxicity.Circulation.2013;127(16):1677-1691.
[27]Walsh R,Thomson KL,Ware JS,et al.Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples.Genet Med.2017;19(2):192-203.
[28]McNally EM,Mestroni L.Dilated Cardiomyopathy:Genetic Determinants and Mechanisms.Circ Res.2017;121(7):731-748.
[29]Hinson JT,Chopra A,Nafissi N,et al.HEART DISEASE.Titin mutations in iPS cells define sarcomere insufficiency as a cause of dilated cardiomyopathy.Science.2015;349(6251):982-986.
[30]Tian T,Wang J,Wang H,et al.A low prevalence of sarcomeric gene variants in a Chinese cohort with left ventricular non-compaction.Heart Vessels.2015;30(2):258-264.
[31]Kodo K,Ong SG,Jahanbani F,et al.iPSC-derived cardiomyocytes reveal abnormal TGF-βsignalling in left ventricular non-compaction cardiomyopathy.Nat Cell Biol.2016;18(10):1031-1042.
[32]Tanaka A,Yuasa S,Mearini G,et al.Endothelin-1 induces myofibrillar disarray and contractile vector variability in hypertrophic cardiomyopathy-induced pluripotent stem cell-derived cardiomyocytes.J Am Heart Assoc.2014;3(6):e001263.
[33]Buikema JW,Wu SM.Untangling the Biology of Genetic Cardiomyopathies with Pluripotent Stem Cell Disease Models.Curr Cardiol Rep.2017;19(4):30.
[34]Wang G,McCain ML,Yang L,et al.Modeling the mitochondrial cardiomyopathy of Barth syndrome with induced pluripotent stem cell and heart-on-chip technologies.Nat Med.2014;20(6):616-623.
[35]Robertson C,Tran DD,George SC.Concise review:maturation phases of human pluripotent stem cell-derived cardiomyocytes.Stem Cells.2013;31(5):829-837.
[36]Asimaki A,Kapoor S,Plovie E,et al.Identification of a new modulator of the intercalated disc in a zebrafish model of arrhythmogenic cardiomyopathy.Sci Transl Med.2014;6(240):240ra74.
[37]Wang Y,Liang P,Lan F,et al.Genome editing of isogenic human induced pluripotent stem cells recapitulates long QTphenotype for drug testing.J Am Coll Cardiol.2014;64(5):451-459.
[38]Lahti AL,Kujala VJ,Chapman H,et al.Model for long QTsyndrome type 2 using human iPS cells demonstrates arrhythmogenic characteristics in cell culture.Dis Model Mech.2012;5(2):220-230.
[39]Itzhaki I,Maizels L,Huber I,et al.Modelling the long QTsyndrome with induced pluripotent stem cells.Nature.2011;471(7337):225-229.
[40]Davis RP,Casini S,van den Berg CW,et al.Cardiomyocytes derived from pluripotent stem cells recapitulate electrophysiological characteristics of an overlap syndrome of cardiac sodium channel disease.Circulation.2012;125(25):3079-3091.
[41]Yazawa M,Hsueh B,Jia X,et al.Using induced pluripotent stem cells to investigate cardiac phenotypes in Timothy syndrome.Nature.2011;471(7337):230-234.
[42]Rocchetti M,Sala L,Dreizehnter L,et al.Elucidating arrhythmogenic mechanisms of long-QT syndrome CALM1-F142L mutation in patient-specific induced pluripotent stem cell-derived cardiomyocytes.Cardiovasc Res.2017;113(5):531-541.
[43]Limpitikul WB,Dick IE,Tester DJ,et al.A Precision Medicine Approach to the Rescue of Function on Malignant Calmodulinopathic Long-QT Syndrome.Circ Res.2017;120(1):39-48.
[44]Lodola F,Morone D,Denegri M,et al.Adeno-associated virus-mediated CASQ2 delivery rescues phenotypic alterations in a patient-specific model of recessive catecholaminergic polymorphic ventricular tachycardia.Cell Death Dis.2016;7(10):e2393.
[45]Sasaki K,Makiyama T,Yoshida Y,et al.Patient-Specific Human Induced Pluripotent Stem Cell Model Assessed with Electrical Pacing Validates S107 as a Potential Therapeutic Agent for Catecholaminergic Polymorphic Ventricular Tachycardia.PLoS One.2016;11(10):e0164795.
[46]Zhang F,Song G,Li X,et al.Transplantation of iPSc ameliorates neural remodeling and reduces ventricular arrhythmias in a post-infarcted swine model.J Cell Biochem.2014;115(3):531-539.
[47]Kitaguchi T,Moriyama Y,Taniguchi T,et al.CSAHi study:Detection of drug-induced ion channel/receptor responses,QT prolongation,and arrhythmia using multi-electrode arrays in combination with human induced pluripotent stem cell-derived cardiomyocytes.J Pharmacol Toxicol Methods.2017;85:73-81.
[48]Mason D,Chen YZ,Krishnan HV,et al.Cardiac gene therapy:Recent advances and future directions.J Control Release.2015;215:101-111.
[49]Shiba Y,Fernandes S,Zhu WZ,et al.Human ES-cell-derived cardiomyocytes electrically couple and suppress arrhythmias in injured hearts.Nature.2012;489(7415):322-325.
[50]van Laake LW,Passier R,Monshouwer-Kloots J,et al.Human embryonic stem cell-derived cardiomyocytes survive and mature in the mouse heart and transiently improve function after myocardial infarction.Stem Cell Res.2007;1(1):9-24.
[51]MenaschéP,Vanneaux V,Hagège A,et al.Human embryonic stem cell-derived cardiac progenitors for severe heart failure treatment:first clinical case report.Eur Heart J.2015;36(30):2011-2017.
[52]MenaschéP,Vanneaux V,Fabreguettes JR,et al.Towards a clinical use of human embryonic stem cell-derived cardiac progenitors:a translational experience.Eur Heart J.2015;36(12):743-750.
[53]Stillitano F,Hansen J,Kong CW,et al.Modeling susceptibility to drug-induced long QT with a panel of subject-specific induced pluripotent stem cells.Elife.2017;6:e19406.
[54]Burridge PW,Li YF,Matsa E,et al.Human induced pluripotent stem cell-derived cardiomyocytes recapitulate the predilection of breast cancer patients to doxorubicin-induced cardiotoxicity.Nat Med.2016;22(5):547-556.
[55]Maddah M,Heidmann JD,Mandegar MA,et al.Anon-invasive platform for functional characterization of stem-cell-derived cardiomyocytes with applications in cardiotoxicity testing.Stem Cell Reports.2015;4(4):621-631.
[56]Doke SK,Dhawale SC.Alternatives to animal testing:Areview.Saudi Pharm J.2015;23(3):223-229.
[57]Freyman T,Polin G,Osman H,et al.A quantitative,randomized study evaluating three methods of mesenchymal stem cell delivery following myocardial infarction.Eur Heart J.2006;27(9):1114-1122.
[58]Cai H,Lin L,Cai H,et al.Prognostic evaluation of microRNA-210 expression in pediatric osteosarcoma.Med Oncol.2013;30(2):499.
[59]Mah N,Wang Y,Liao MC,et al.Molecular insights into reprogramming-initiation events mediated by the OSKM gene regulatory network.PLoS One.2011;6(8):e24351.
[60]Gintant G,Sager PT,Stockbridge N.Evolution of strategies to improve preclinical cardiac safety testing.Nat Rev Drug Discov.2016;15(7):457-471.
[2]Go AS,Mozaffarian D,Roger VL,et al.Heart disease and stroke statistics--2013 update:a report from the American Heart Association.Circulation.2013;127(1):e6-e245.
[3]GBD 2013 Risk Factors Collaborators,Forouzanfar MH,Alexander L,et al.Global,regional,and national comparative risk assessment of 79 behavioural,environmental and occupational,and metabolic risks or clusters of risks in 188countries,1990-2013:a systematic analysis for the Global Burden of Disease Study 2013.Lancet.2015;386(10010):2287-2323.
[4]Chen CH,Sereti KI,Wu BM,et al.Translational aspects of cardiac cell therapy.J Cell Mol Med.2015;19(8):1757-1772.
[5]Pagidipati NJ,Gaziano TA.Estimating deaths from cardiovascular disease:a review of global methodologies of mortality measurement.Circulation.2013;127(6):749-756.
[6]Bergmann O,Bhardwaj RD,Bernard S,et al.Evidence for cardiomyocyte renewal in humans.Science.2009;324(5923):98-102.
[7]Lalit PA,Hei DJ,Raval AN,et al.Induced pluripotent stem cells for post-myocardial infarction repair:remarkable opportunities and challenges.Circ Res.2014;114(8):1328-1345.
[8]Okano H,Nakamura M,Yoshida K,et al.Steps toward safe cell therapy using induced pluripotent stem cells.Circ Res.2013;112(3):523-533.
[9]Takahashi K,Tanabe K,Ohnuki M,et al.Induction of pluripotent stem cells from adult human fibroblasts by defined factors.Cell.2007;131(5):861-872.
[10]Takahashi K,Yamanaka S.Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.Cell.2006;126(4):663-676.
[11]Okita K,Ichisaka T,Yamanaka S.Generation of germlinecompetent induced pluripotent stem cells.Nature.2007;448(7151):313-317.
[12]Yu T,Miyagawa S,Miki K,et al.In vivo differentiation of induced pluripotent stem cell-derived cardiomyocytes.Circ J.2013;77(5):1297-1306.
[13]Mandai M,Watanabe A,Kurimoto Y,et al.Autologous Induced Stem-Cell-Derived Retinal Cells for Macular Degeneration.N Engl J Med.2017;376(11):1038-1046.
[14]Sayed N,Liu C,Wu JC.Translation of Human-Induced Pluripotent Stem Cells:From Clinical Trial in a Dish to Precision Medicine.J Am Coll Cardiol.2016;67(18):2161-2176.
[15]Nam YJ,Song K,Luo X,et al.Reprogramming of human fibroblasts toward a cardiac fate.Proc Natl Acad Sci U S A.2013;110(14):5588-5593.
[16]Qian L,Huang Y,Spencer CI,et al.In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes.Nature.2012;485(7400):593-598.
[17]DidiéM,Christalla P,Rubart M,et al.Parthenogenetic stem cells for tissue-engineered heart repair.J Clin Invest.2013;123(3):1285-1298.
[18]Riegler J,Tiburcy M,Ebert A,et al.Human Engineered Heart Muscles Engraft and Survive Long Term in a Rodent Myocardial Infarction Model.Circ Res.2015;117(8):720-730.
[19]Ong SG,Huber BC,Lee WH,et al.Microfluidic Single-Cell Analysis of Transplanted Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes After Acute Myocardial Infarction.Circulation.2015;132(8):762-771.
[20]Chong JJ,Yang X,Don CW,et al.Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts.Nature.2014;510(7504):273-277.
[21]Kawamura M,Miyagawa S,Fukushima S,et al.Enhanced survival of transplanted human induced pluripotent stem cell-derived cardiomyocytes by the combination of cell sheets with the pedicled omental flap technique in a porcine heart.Circulation.2013;128(11 Suppl 1):S87-94.
[22]Ye L,Chang YH,Xiong Q,et al.Cardiac repair in a porcine model of acute myocardial infarction with human induced pluripotent stem cell-derived cardiovascular cells.Cell Stem Cell.2014;15(6):750-761.
[23]Shiba Y,Gomibuchi T,Seto T,et al.Allogeneic transplantation of iPS cell-derived cardiomyocytes regenerates primate hearts.Nature.2016;538(7625):388-391.
[24]Lan F,Lee AS,Liang P,et al.Abnormal calcium handling properties underlie familial hypertrophic cardiomyopathy pathology in patient-specific induced pluripotent stem cells.Cell Stem Cell.2013;12(1):101-113.
[25]Wu H,Lee J,Vincent LG,et al.Epigenetic Regulation of Phosphodiesterases 2A and 3A Underlies Compromisedβ-Adrenergic Signaling in an iPSC Model of Dilated Cardiomyopathy.Cell Stem Cell.2015;17(1):89-100.
[26]Liang P,Lan F,Lee AS,et al.Drug screening using a library of human induced pluripotent stem cell-derived cardiomyocytes reveals disease-specific patterns of cardiotoxicity.Circulation.2013;127(16):1677-1691.
[27]Walsh R,Thomson KL,Ware JS,et al.Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples.Genet Med.2017;19(2):192-203.
[28]McNally EM,Mestroni L.Dilated Cardiomyopathy:Genetic Determinants and Mechanisms.Circ Res.2017;121(7):731-748.
[29]Hinson JT,Chopra A,Nafissi N,et al.HEART DISEASE.Titin mutations in iPS cells define sarcomere insufficiency as a cause of dilated cardiomyopathy.Science.2015;349(6251):982-986.
[30]Tian T,Wang J,Wang H,et al.A low prevalence of sarcomeric gene variants in a Chinese cohort with left ventricular non-compaction.Heart Vessels.2015;30(2):258-264.
[31]Kodo K,Ong SG,Jahanbani F,et al.iPSC-derived cardiomyocytes reveal abnormal TGF-βsignalling in left ventricular non-compaction cardiomyopathy.Nat Cell Biol.2016;18(10):1031-1042.
[32]Tanaka A,Yuasa S,Mearini G,et al.Endothelin-1 induces myofibrillar disarray and contractile vector variability in hypertrophic cardiomyopathy-induced pluripotent stem cell-derived cardiomyocytes.J Am Heart Assoc.2014;3(6):e001263.
[33]Buikema JW,Wu SM.Untangling the Biology of Genetic Cardiomyopathies with Pluripotent Stem Cell Disease Models.Curr Cardiol Rep.2017;19(4):30.
[34]Wang G,McCain ML,Yang L,et al.Modeling the mitochondrial cardiomyopathy of Barth syndrome with induced pluripotent stem cell and heart-on-chip technologies.Nat Med.2014;20(6):616-623.
[35]Robertson C,Tran DD,George SC.Concise review:maturation phases of human pluripotent stem cell-derived cardiomyocytes.Stem Cells.2013;31(5):829-837.
[36]Asimaki A,Kapoor S,Plovie E,et al.Identification of a new modulator of the intercalated disc in a zebrafish model of arrhythmogenic cardiomyopathy.Sci Transl Med.2014;6(240):240ra74.
[37]Wang Y,Liang P,Lan F,et al.Genome editing of isogenic human induced pluripotent stem cells recapitulates long QTphenotype for drug testing.J Am Coll Cardiol.2014;64(5):451-459.
[38]Lahti AL,Kujala VJ,Chapman H,et al.Model for long QTsyndrome type 2 using human iPS cells demonstrates arrhythmogenic characteristics in cell culture.Dis Model Mech.2012;5(2):220-230.
[39]Itzhaki I,Maizels L,Huber I,et al.Modelling the long QTsyndrome with induced pluripotent stem cells.Nature.2011;471(7337):225-229.
[40]Davis RP,Casini S,van den Berg CW,et al.Cardiomyocytes derived from pluripotent stem cells recapitulate electrophysiological characteristics of an overlap syndrome of cardiac sodium channel disease.Circulation.2012;125(25):3079-3091.
[41]Yazawa M,Hsueh B,Jia X,et al.Using induced pluripotent stem cells to investigate cardiac phenotypes in Timothy syndrome.Nature.2011;471(7337):230-234.
[42]Rocchetti M,Sala L,Dreizehnter L,et al.Elucidating arrhythmogenic mechanisms of long-QT syndrome CALM1-F142L mutation in patient-specific induced pluripotent stem cell-derived cardiomyocytes.Cardiovasc Res.2017;113(5):531-541.
[43]Limpitikul WB,Dick IE,Tester DJ,et al.A Precision Medicine Approach to the Rescue of Function on Malignant Calmodulinopathic Long-QT Syndrome.Circ Res.2017;120(1):39-48.
[44]Lodola F,Morone D,Denegri M,et al.Adeno-associated virus-mediated CASQ2 delivery rescues phenotypic alterations in a patient-specific model of recessive catecholaminergic polymorphic ventricular tachycardia.Cell Death Dis.2016;7(10):e2393.
[45]Sasaki K,Makiyama T,Yoshida Y,et al.Patient-Specific Human Induced Pluripotent Stem Cell Model Assessed with Electrical Pacing Validates S107 as a Potential Therapeutic Agent for Catecholaminergic Polymorphic Ventricular Tachycardia.PLoS One.2016;11(10):e0164795.
[46]Zhang F,Song G,Li X,et al.Transplantation of iPSc ameliorates neural remodeling and reduces ventricular arrhythmias in a post-infarcted swine model.J Cell Biochem.2014;115(3):531-539.
[47]Kitaguchi T,Moriyama Y,Taniguchi T,et al.CSAHi study:Detection of drug-induced ion channel/receptor responses,QT prolongation,and arrhythmia using multi-electrode arrays in combination with human induced pluripotent stem cell-derived cardiomyocytes.J Pharmacol Toxicol Methods.2017;85:73-81.
[48]Mason D,Chen YZ,Krishnan HV,et al.Cardiac gene therapy:Recent advances and future directions.J Control Release.2015;215:101-111.
[49]Shiba Y,Fernandes S,Zhu WZ,et al.Human ES-cell-derived cardiomyocytes electrically couple and suppress arrhythmias in injured hearts.Nature.2012;489(7415):322-325.
[50]van Laake LW,Passier R,Monshouwer-Kloots J,et al.Human embryonic stem cell-derived cardiomyocytes survive and mature in the mouse heart and transiently improve function after myocardial infarction.Stem Cell Res.2007;1(1):9-24.
[51]MenaschéP,Vanneaux V,Hagège A,et al.Human embryonic stem cell-derived cardiac progenitors for severe heart failure treatment:first clinical case report.Eur Heart J.2015;36(30):2011-2017.
[52]MenaschéP,Vanneaux V,Fabreguettes JR,et al.Towards a clinical use of human embryonic stem cell-derived cardiac progenitors:a translational experience.Eur Heart J.2015;36(12):743-750.
[53]Stillitano F,Hansen J,Kong CW,et al.Modeling susceptibility to drug-induced long QT with a panel of subject-specific induced pluripotent stem cells.Elife.2017;6:e19406.
[54]Burridge PW,Li YF,Matsa E,et al.Human induced pluripotent stem cell-derived cardiomyocytes recapitulate the predilection of breast cancer patients to doxorubicin-induced cardiotoxicity.Nat Med.2016;22(5):547-556.
[55]Maddah M,Heidmann JD,Mandegar MA,et al.Anon-invasive platform for functional characterization of stem-cell-derived cardiomyocytes with applications in cardiotoxicity testing.Stem Cell Reports.2015;4(4):621-631.
[56]Doke SK,Dhawale SC.Alternatives to animal testing:Areview.Saudi Pharm J.2015;23(3):223-229.
[57]Freyman T,Polin G,Osman H,et al.A quantitative,randomized study evaluating three methods of mesenchymal stem cell delivery following myocardial infarction.Eur Heart J.2006;27(9):1114-1122.
[58]Cai H,Lin L,Cai H,et al.Prognostic evaluation of microRNA-210 expression in pediatric osteosarcoma.Med Oncol.2013;30(2):499.
[59]Mah N,Wang Y,Liao MC,et al.Molecular insights into reprogramming-initiation events mediated by the OSKM gene regulatory network.PLoS One.2011;6(8):e24351.
[60]Gintant G,Sager PT,Stockbridge N.Evolution of strategies to improve preclinical cardiac safety testing.Nat Rev Drug Discov.2016;15(7):457-471.