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Cell Reprogramming for Cardiac Regeneration and Rare Disease Modeling

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Book cover Cell Therapy

Part of the book series: Molecular and Translational Medicine ((MOLEMED))

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Abstract

The field of regenerative medicine has made great progress with the development of cell reprogramming and gene editing techniques. The option to derive pluripotent cells from somatic cells by overexpression of pluripotent factors or specific molecules, and even more the possibility to reprogram one somatic cell type to another somatic cell type in vitro and in vivo, has offered many new options for future therapies.

In this chapter, we provide an overview of the studies performed to understand the mechanisms and to develop the techniques for cell reprogramming, focusing specially in their application in cardiac regeneration and rare disease modeling. First, we discuss the plasticity of cells and methods for their reprogramming. Also, a description of the different studies for differentiation of pluripotent cells toward cardiovascular cells and direct cell reprogramming is provided. Finally, the use of reprogrammed cells as a model for human pathologies, mainly rare diseases, the different aspects that should be bear in mind for optimal model development, the use of gene editing for creating novel and improved disease models, and the therapeutic applications of iPSC-based models have been thoroughly described in this chapter.

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References

  1. Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KH. Viable offspring derived from fetal and adult mammalian cells. Nature. 1997;385:810–3.

    Article  CAS  PubMed  Google Scholar 

  2. Yamanaka S, Blau HM. Nuclear reprogramming to a pluripotent state by three approaches. Nature. 2010;465:704–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126:663–76.

    Article  CAS  PubMed  Google Scholar 

  4. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131:861–72.

    Article  CAS  PubMed  Google Scholar 

  5. Yu J, Vodyanik MA, Smuga-Otto K, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007;318:1917–20.

    Article  CAS  PubMed  Google Scholar 

  6. Okita K, Ichisaka T, Yamanaka S. Generation of germline-competent induced pluripotent stem cells. Nature. 2007;448:313–7.

    Article  CAS  PubMed  Google Scholar 

  7. Fonseca SAS, Costas RM, Pereira LV. Searching for naïve human pluripotent stem cells. World J Stem Cells. 2015;7:649–56.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Takahashi K, Yamanaka S. A decade of transcription factor-mediated reprogramming to pluripotency. Nat Rev Mol Cell Biol. 2016;17:183–93.

    Article  CAS  PubMed  Google Scholar 

  9. Kim JB, Greber B, Araúzo-Bravo MJ, Meyer J, Park KI, Zaehres H, Schöler HR. Direct reprogramming of human neural stem cells by OCT4. Nature. 2009;461:649–3.

    Article  CAS  PubMed  Google Scholar 

  10. González F, Boué S, Izpisúa Belmonte JC. Methods for making induced pluripotent stem cells: reprogramming à la carte. Nat Rev Genet. 2011;12:231–42.

    Article  PubMed  CAS  Google Scholar 

  11. Niwa H, Burdon T, Chambers I, Smith A. Self-renewal of pluripotent embryonic stem cells is mediated via activation of STAT3. Genes Dev. 1998;12:2048–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Xiao L, Yuan X, Sharkis SJ. Activin A maintains self-renewal and regulates fibroblast growth factor, Wnt, and bone morphogenic protein pathways in human embryonic stem cells. Stem Cells. 2006;24:1476–86.

    Article  CAS  PubMed  Google Scholar 

  13. Chen Y, Niu Y, Li Y, et al. Generation of Cynomolgus monkey chimeric fetuses using embryonic stem cells. Cell Stem Cell. 2015;17:116–24.

    Article  CAS  PubMed  Google Scholar 

  14. Usui J, Kobayashi T, Yamaguchi T, Knisely AS, Nishinakamura R, Nakauchi H. Generation of kidney from pluripotent stem cells via blastocyst complementation. Am J Pathol. 2012;180:2417–26.

    Article  CAS  PubMed  Google Scholar 

  15. Kobayashi T, Yamaguchi T, Hamanaka S, et al. Generation of rat pancreas in mouse by interspecific blastocyst injection of pluripotent stem cells. Cell. 2010;142:787–99.

    Article  CAS  PubMed  Google Scholar 

  16. Davis RL, Weintraub H, Lassar AB. Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell. 1987;51:987–1000.

    Article  CAS  PubMed  Google Scholar 

  17. Kulessa H, Frampton J, Graf T. GATA-1 reprograms avian myelomonocytic cell lines into eosinophils, thromboblasts, and erythroblasts. Genes Dev. 1995;9:1250–62.

    Article  CAS  PubMed  Google Scholar 

  18. Bar-Nur O, Verheul C, Sommer AG, Brumbaugh J, Schwarz BA, Lipchina I, Huebner AJ, Mostoslavsky G, Hochedlinger K. Lineage conversion induced by pluripotency factors involves transient passage through an iPSC stage. Nat Biotechnol. 2015;33:761–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Maza I, Caspi I, Zviran A, et al. Transient acquisition of pluripotency during somatic cell transdifferentiation with iPSC reprogramming factors. Nat Biotechnol. 2015;33:769–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Efe JA, Hilcove S, Kim J, Zhou H, Ouyang K, Wang G, Chen J, Ding S. Conversion of mouse fibroblasts into cardiomyocytes using a direct reprogramming strategy. Nat Cell Biol. 2011;13:215–22.

    Article  CAS  PubMed  Google Scholar 

  21. Sadahiro T, Yamanaka S, Ieda M. Direct cardiac reprogramming: progress and challenges in basic biology and clinical applications. Circ Res. 2015;116:1378–91.

    Article  CAS  PubMed  Google Scholar 

  22. Li H, Chen G. In vivo reprogramming for CNS repair: regenerating neurons from endogenous glial cells. Neuron. 2016;91:728–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Qian L, Huang Y, Spencer CI, et al. HHS public. Access. 2012;485:593–8.

    CAS  Google Scholar 

  24. Song K, Nam Y-J, Luo X, et al. Heart repair by reprogramming non-myocytes with cardiac transcription factors. Nature. 2012;485:599–604.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Garber K. RIKEN suspends first clinical trial involving induced pluripotent stem cells. Nat Biotechnol. 2015;33:890–1.

    Article  CAS  PubMed  Google Scholar 

  26. Singh VK, Kalsan M, Kumar N, Saini A, Chandra R. Induced pluripotent stem cells: applications in regenerative medicine, disease modeling, and drug discovery. Front Cell Dev Biol. 2015;3:2.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Robinton DA, Daley GQ. The promise of induced pluripotent stem cells in research and therapy. Nature. 2012;481:295–305.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Tiscornia G, Vivas EL, Belmonte JCI. Diseases in a dish: modeling human genetic disorders using induced pluripotent cells. Nat Med. 2011;17:1570–6.

    Article  CAS  PubMed  Google Scholar 

  29. Laube F, Heister M, Scholz C, Borchardt T, Braun T. Re-programming of newt cardiomyocytes is induced by tissue regeneration. J Cell Sci. 2006;119:4719–29.

    Article  CAS  PubMed  Google Scholar 

  30. Jopling C, Sleep E, Raya M, Martí M, Raya A, Izpisúa Belmonte JC. Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation. Nature. 2010;464:606–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Mollova M, Bersell K, Walsh S, et al. Cardiomyocyte proliferation contributes to heart growth in young humans. Proc Natl Acad Sci U S A. 2013;110:1446–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Naqvi N, Li M, Calvert JW, et al. A proliferative burst during preadolescence establishes the final cardiomyocyte number. Cell. 2014;157:795–807.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Senyo SE, Steinhauser ML, Pizzimenti CL, Yang VK, Cai L, Wang M, T-D W, Guerquin-Kern J-L, Lechene CP, Lee RT. Mammalian heart renewal by pre-existing cardiomyocytes. Nature. 2013;493:433–6.

    Article  CAS  PubMed  Google Scholar 

  34. Hsieh PCH, Segers VFM, Davis ME, MacGillivray C, Gannon J, Molkentin JD, Robbins J, Lee RT. Evidence from a genetic fate-mapping study that stem cells refresh adult mammalian cardiomyocytes after injury. Nat Med. 2007;13:970–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Laflamme MA, Murry CE. Heart regeneration. Nature. 2011;473:326–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Reardon S. New life for pig-to-human transplants. Nature. 2015;527:152–4.

    Article  CAS  PubMed  Google Scholar 

  37. Sahara M, Santoro F, Chien KR. Programming and reprogramming a human heart cell. EMBO J. 2015;34:710–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Rosen MR, Myerburg RJ, Francis DP, Cole GD, Marbán E. Translating stem cell research to cardiac disease therapies: pitfalls and prospects for improvement. J Am Coll Cardiol. 2014;64:922–37.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Gerbin KA, Murry CE. The winding road to regenerating the human heart. Cardiovasc Pathol. 2015;24:133–40.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Prowse ABJ, Timmins NE, Yau TM, Li R-K, Weisel RD, Keller G, Zandstra PW. Transforming the promise of pluripotent stem cell-derived cardiomyocytes to a therapy: challenges and solutions for clinical trials. Can J Cardiol. 2014;30:1335–49.

    Article  PubMed  Google Scholar 

  41. Limbourg FP, Ringes-Lichtenberg S, Schaefer A, et al. Haematopoietic stem cells improve cardiac function after infarction without permanent cardiac engraftment. Eur J Heart Fail. 2005;7:722–9.

    Article  CAS  PubMed  Google Scholar 

  42. Davis DR, Zhang Y, Smith RR, Cheng K, Terrovitis J, Malliaras K, Li T-S, White A, Makkar R, Marbán E. Validation of the cardiosphere method to culture cardiac progenitor cells from myocardial tissue. PLoS One. 2009;4:e7195.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Itskovitz-Eldor J, Schuldiner M, Karsenti D, Eden A, Yanuka O, Amit M, Soreq H, Benvenisty N. Differentiation of human embryonic stem cells into embryoid bodies compromising the three embryonic germ layers. Mol Med. 2000;6:88–95.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Mummery CL, Zhang J, Ng ES, Elliott DA, Elefanty AG, Kamp TJ. Differentiation of human embryonic stem cells and induced pluripotent stem cells to cardiomyocytes: a methods overview. Circ Res. 2012;111:344–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Kattman SJ, Witty AD, Gagliardi M, Dubois NC, Niapour M, Hotta A, Ellis J, Keller G. Stage-specific optimization of activin/nodal and BMP signaling promotes cardiac differentiation of mouse and human pluripotent stem cell lines. Cell Stem Cell. 2011;8:228–40.

    Article  CAS  PubMed  Google Scholar 

  46. Bauwens CL, Peerani R, Niebruegge S, Woodhouse KA, Kumacheva E, Husain M, Zandstra PW. Control of human embryonic stem cell colony and aggregate size heterogeneity influences differentiation trajectories. Stem Cells. 2008;26:2300–10.

    Article  PubMed  Google Scholar 

  47. Zhu WZ, Van Biber B, Laflamme MA. Methods for the derivation and use of cardiomyocytes from human pluripotent stem cells. Methods Mol Biol. 2011;767:419–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Uosaki H, Fukushima H, Takeuchi A, Matsuoka S, Nakatsuji N, Yamanaka S, Yamashita JK. Efficient and scalable purification of cardiomyocytes from human embryonic and induced pluripotent stem cells by VCAM1 surface expression. PLoS One. 2011;6:e23657.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Kita-Matsuo H, Barcova M, Prigozhina N, et al. Lentiviral vectors and protocols for creation of stable hESC lines for fluorescent tracking and drug resistance selection of cardiomyocytes. PLoS One. 2009;4:e5046.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Chong JJH, Yang X, Don CW, et al. Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts. Nature. 2014;510:273–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Taura D, Sone M, Homma K, Oyamada N, Takahashi K, Tamura N, Yamanaka S, Nakao K. Induction and isolation of vascular cells from human induced pluripotent stem cells—brief report. Arterioscler Thromb Vasc Biol. 2009;29:1100–3.

    Article  CAS  PubMed  Google Scholar 

  52. Lin B, Kim J, Li Y, Pan H, Carvajal-Vergara X, Salama G, Cheng T, Li Y, Lo CW, Yang L. High-purity enrichment of functional cardiovascular cells from human iPS cells. Cardiovasc Res. 2012;95:327–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Staton CA, Reed MWR, Brown NJ. A critical analysis of current in vitro and in vivo angiogenesis assays. Int J Exp Pathol. 2009;90:195–221.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Gu M, Nguyen PK, Lee AS, et al. Microfluidic single-cell analysis shows that porcine induced pluripotent stem cell–derived endothelial cells improve myocardial function by paracrine activation novelty and significance. Circ Res. 2012;111:882–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Carvajal-Vergara X, Prósper F. Are we closer to cardiac regeneration? Stem Cell Investig. 2016;3:59.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Menasché P, 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;36:2011–7.

    Article  PubMed  Google Scholar 

  57. Bellamy V, Vanneaux V, Bel A, et al. Long-term functional benefits of human embryonic stem cell-derived cardiac progenitors embedded into a fibrin scaffold. J Heart Lung Transplant. 2015;34:1198–207.

    Article  PubMed  Google Scholar 

  58. Kervadec A, Bellamy V, El Harane N, et al. Cardiovascular progenitor-derived extracellular vesicles recapitulate the beneficial effects of their parent cells in the treatment of chronic heart failure. J Heart Lung Transplant. 2016;35:795–807.

    Article  PubMed  Google Scholar 

  59. Wang H, Cao N, Spencer CI, Nie B, Ma T, Xu T, Zhang Y, Wang X, Srivastava D, Ding S. Small molecules enable cardiac reprogramming of mouse fibroblasts with a single factor, Oct 4. Cell Rep. 2014;6:951–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Li J, Huang NF, Zou J, Laurent TJ, Lee JC, Okogbaa J, Cooke JP, Ding S. Conversion of human fibroblasts to functional endothelial cells by defined factors. Arterioscler Thromb Vasc Biol. 2013;33:1366–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Margariti A, Winkler B, Karamariti E, et al. Direct reprogramming of fibroblasts into endothelial cells capable of angiogenesis and reendothelialization in tissue-engineered vessels. Proc Natl Acad Sci U S A. 2012;109:13793–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Zhao Y, Londono P, Cao Y, et al. High-efficiency reprogramming of fibroblasts into cardiomyocytes requires suppression of pro-fibrotic signalling. Nat Commun. 2015;6:8243.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Cao N, Huang Y, Zheng J, et al. Conversion of human fibroblasts into functional cardiomyocytes by small molecules. Science. 2016;352:aaf1502.

    Article  CAS  Google Scholar 

  64. Han JK, Chang SH, Cho HJ, et al. Direct conversion of adult skin fibroblasts to endothelial cells by defined factors. Circulation. 2014;130:1168–78.

    Article  CAS  PubMed  Google Scholar 

  65. Wong WT, Cooke JP. Therapeutic transdifferentiation of human fibroblasts into endothelial cells using forced expression of lineage-specific transcription factors. J Tissue Eng. 2016;7:2041731416628329.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Van Pham P, NB V, Nguyen HT, et al. Significant improvement of direct reprogramming efficacy of fibroblasts into progenitor endothelial cells by ETV2 and hypoxia. Stem Cell Res Ther. 2016;7:104.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Islas JF, Liu Y, Weng K-C, et al. Transcription factors ETS2 and MESP1 transdifferentiate human dermal fibroblasts into cardiac progenitors. Proc Natl Acad Sci U S A. 2012;109:13016–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Lalit PA, Salick MR, Nelson DO, et al. Lineage reprogramming of fibroblasts into proliferative induced cardiac progenitor cells by defined factors. Cell Stem Cell. 2016;18:354–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Muraoka N, Ieda M. Direct reprogramming of fibroblasts into myocytes to reverse fibrosis. Annu Rev Physiol. 2014;76:21–37.

    Article  CAS  PubMed  Google Scholar 

  70. Yamakawa H, Ieda M. Strategies for heart regeneration. Int Heart J. 2015;56:1–5.

    Article  PubMed  Google Scholar 

  71. 107th Congress of the United States of America. Rare Diseases Act of 2002. 2002. p. 1–5.

    Google Scholar 

  72. European Commission. Useful Information on rare diseases from an EU perspective. 2005. p. 2005–2006.

    Google Scholar 

  73. Avior Y, Sagi I, Benvenisty N. Pluripotent stem cells in disease modelling and drug discovery. Nat Rev Mol Cell Biol. 2016;17:170–82.

    Article  CAS  PubMed  Google Scholar 

  74. Sterneckert JL, Reinhardt P, Scholer HR. Investigating human disease using stem cell models. Nat Rev Genet. 2014;15:625–39.

    Article  CAS  PubMed  Google Scholar 

  75. Chen KG, Mallon BS, McKay RDG, Robey PG. Human pluripotent stem cell culture: considerations for maintenance, expansion, and therapeutics. Cell Stem Cell. 2014;14:13–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Sun N, Longaker MT, JC W. Human iPS cell-based therapy: considerations before clinical applications. Cell Cycle. 2010;9:880. –885

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Zapata-Linares N, Rodriguez S, Salido E, Abizanda G, Iglesias E, Prosper F, Gonzalez-Aseguinolaza G, Rodriguez-Madoz JR. Generation and characterization of human iPSC lines derived from a Primary Hyperoxaluria Type I patient with p.I244T mutation. Stem Cell Res. 2016;16:116–9.

    Article  CAS  PubMed  Google Scholar 

  78. Raya A, Rodríguez-Pizà I, Guenechea G, et al. Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells. Nature. 2009;460:53–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Lemonnier T, Blanchard S, Toli D, Roy E, Bigou S, Froissart R, Rouvet I, Vitry S, Heard JM, Bohl D. Modeling neuronal defects associated with a lysosomal disorder using patient-derived induced pluripotent stem cells. Hum Mol Genet. 2011;20:3653–66.

    Article  CAS  PubMed  Google Scholar 

  80. Park I-H. Disease-specific induced pluripotent stem cells. Cell. 2008;134:877–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Ebert AD, Yu J, Rose FF, Mattis VB, Lorson CL, Thomson JA, Svendsen CN. Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature. 2009;457:277–80.

    Article  CAS  PubMed  Google Scholar 

  82. Carvajal-Vergara X, Sevilla A, D’Souza SL, et al. Patient-specific induced pluripotent stem-cell-derived models of LEOPARD syndrome. Nature. 2010;465:808–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Moretti A, Bellin M, Welling A, et al. Patient-specific induced pluripotent stem-cell models for Long-QT syndrome. N Engl J Med. 2010;363:1397–409.

    Article  CAS  PubMed  Google Scholar 

  84. Itzhaki I, Maizels L, Huber I, et al. Modelling the long QT syndrome with induced pluripotent stem cells. Nature. 2011;471:225–9.

    Article  CAS  PubMed  Google Scholar 

  85. Zhang S, Chen S, Li W, et al. Rescue of ATP7B function in hepatocyte-like cells from Wilson’s disease induced pluripotent stem cells using gene therapy or the chaperone drug curcumin. Hum Mol Genet. 2011;20:3176–87.

    Article  CAS  PubMed  Google Scholar 

  86. Yusa K, Rashid ST, Strick-Marchand H, et al. Targeted gene correction of α1-antitrypsin deficiency in induced pluripotent stem cells. Nature. 2011;478:391–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Ye Z, Zhan H, Dowey S, Williams DM, Jang Y, Dang CV, Spivak JL, Moliterno AR, Cheng L, Mali P. Human-induced pluripotent stem cells from blood cells of healthy donors and patients with acquired blood disorders. Blood Cells. 2009;114:5473–80.

    Article  CAS  Google Scholar 

  88. Burkhardt MF, Martinez FJ, Wright S, et al. A cellular model for sporadic ALS using patient-derived induced pluripotent stem cells. Mol Cell Neurosci. 2013;56:355–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Kim JJ. Applications of iPSCs in cancer research. Biomark Insights. 2015;10:125.

    Article  PubMed  PubMed Central  Google Scholar 

  90. Germain ND, Chen P-F, Plocik AM, et al. Gene expression analysis of human induced pluripotent stem cell-derived neurons carrying copy number variants of chromosome 15q11-q13.1. Mol Autism. 2014;5:44.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  91. Hibaoui Y, Grad I, Letourneau A, et al. Modelling and rescuing neurodevelopmental defect of Down syndrome using induced pluripotent stem cells from monozygotic twins discordant for trisomy 21. EMBO Mol Med. 2014;6:259–77.

    CAS  PubMed  Google Scholar 

  92. Sagie S, Ellran E, Katzir H, Shaked R, Yehezkel S, Laevsky I, Ghanayim A, Geiger D, Tzukerman M, Selig S. Induced pluripotent stem cells as a model for telomeric abnormalities in ICF type I syndrome. Hum Mol Genet. 2014;23:3629–40.

    Article  CAS  PubMed  Google Scholar 

  93. Stelzer Y, Sagi I, Yanuka O, Eiges R, Benvenisty N. The noncoding RNA IPW regulates the imprinted DLK1-DIO3 locus in an induced pluripotent stem cell model of Prader-Willi syndrome. Nat Genet. 2014;46:551–7.

    Article  CAS  PubMed  Google Scholar 

  94. Gaj T, Gersbach CA, Barbas CF. ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends Biotechnol. 2013;31:397–405.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Hockemeyer D, Jaenisch R. Induced pluripotent stem cells meet genome editing. Cell Stem Cell. 2016;18:573–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Hendriks WT, Warren CR, Cowan CA. Genome editing in human pluripotent stem cells: approaches, pitfalls, and solutions. Cell Stem Cell. 2016;18:53–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Cong L, Ran FA, Cox D, et al. Multiplex genome engineering using CRISPR/Cas system. Science. 2013;339:819–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Corti S, Nizzardo M, Simone C, et al. Genetic correction of human induced pluripotent stem cells from patients with spinal muscular atrophy. Sci Transl Med. 2012;4:165ra162.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  99. Ding Q, Lee YK, Schaefer EAK, et al. A TALEN genome-editing system for generating human stem cell-based disease models. Cell Stem Cell. 2013;12:238–51.

    Article  CAS  PubMed  Google Scholar 

  100. Tai DJC, Ragavendran A, Manavalan P, et al. Engineering microdeletions and microduplications by targeting segmental duplications with CRISPR. Nat Neurosci. 2016;19:517–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Maddalo D, Manchado E, Concepcion CP, et al. In vivo engineering of oncogenic chromosomal rearrangements with the CRISPR/Cas9 system. Nature. 2014;516:423–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Choi SM, Kim Y, Shim JS, Park JT, Wang RH, Leach SD, Liu JO, Deng C, Ye Z, Jang YY. Efficient drug screening and gene correction for treating liver disease using patient-specific stem cells. Hepatology. 2013;57:2458–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Höing S, Rudhard Y, Reinhardt P, et al. Discovery of inhibitors of microglial neurotoxicity acting through multiple mechanisms using a stem-cell-based phenotypic assay. Cell Stem Cell. 2012;11:620–32.

    Article  PubMed  CAS  Google Scholar 

  104. Hanna J, Markoulaki S, Sun CW, Meissner A, Cassady JP, Beard C, Brambrink T, Wu LC, Townes TM, Jaenisch R, Wernig M. Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science. 2007;318:1920–3.

    Article  CAS  PubMed  Google Scholar 

  105. Wernig M, Zhao J-P, Pruszak J, Hedlund E, Fu D, Soldner F, Broccoli V, Constantine-Paton M, Isacson O, Jaenisch R. Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson’s disease. Proc Natl Acad Sci U S A. 2008;105:5856–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Young CS, Hicks MR, Ermolova NV, et al. A single CRISPR-Cas9 deletion strategy that targets the majority of DMD patients restores dystrophin function in hiPSC-derived muscle cells. Cell Stem Cell. 2016;18:533–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Foundation for Applied Medical Research (FIMA), Cell Therapy Program, Av Pio XII, 55, Pamplona, Navarra, 31008, Spain

    Xonia Carvajal-Vergara Ph.D., Juan Roberto Rodríguez-Madoz Ph.D., Beatriz Pelacho Ph.D. & Felipe Prósper M.D.

  2. Hematology and Cell Therapy, Clinica Universidad de Navarra, Av Pio XII, 36, Pamplona, Navarra, 31008, Spain

    Felipe Prósper M.D.

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  1. Xonia Carvajal-Vergara Ph.D.
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    Dwaine F. Emerich

  2. Paseo de la Universidad 7, Vitoria-Gasteiz, Spain

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Carvajal-Vergara, X., Rodríguez-Madoz, J.R., Pelacho, B., Prósper, F. (2017). Cell Reprogramming for Cardiac Regeneration and Rare Disease Modeling. In: Emerich, D., Orive, G. (eds) Cell Therapy. Molecular and Translational Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-57153-9_9

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  • DOI: https://doi.org/10.1007/978-3-319-57153-9_9

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