iPS Cell Modeling of Cardiometabolic Diseases

  • Kenta NakamuraEmail author
  • Ken-ichi Hirano
  • Sean M. WuEmail author


Cardiometabolic diseases encompass simple monogenic enzyme deficiencies with well-established pathogenesis and clinical outcomes to complex polygenic diseases such as the cardiometabolic syndrome. The limited availability of relevant human cell types such as cardiomyocytes has hampered our ability to adequately model and study pathways or drugs relevant to these diseases in the heart. The recent discovery of induced pluripotent stem (iPS) cell technology now offers a powerful opportunity to establish translational platforms for cardiac disease modeling, drug discovery, and pre-clinical testing. In this article, we discuss the excitement and challenges of modeling cardiometabolic diseases using iPS cell and their potential to revolutionize translational research.


Cardiometabolic disease Induced pluripotent stem cell Disease modeling Storage disease 



The authors would like to thank Ms. Karolina Plonowska for her editorial assistance. This work was funded by NIH Officer of the Director and NIH/NHLBI to S.M.W. We apologize for our inability to cite many excellent studies in this area due to space constraints.


  1. 1.
    Evans, M. J., & Kaufman, M. H. (1981). Establishment in culture of pluripotential cells from mouse embryos. Nature, 292(5819), 154–156.PubMedCrossRefGoogle Scholar
  2. 2.
    Thomson, J. A., Itskovitz-Eldor, J., Shapiro, S. S., Waknitz, M. A., Swiergiel, J. J., Marshall, V. S., et al. (1998). Embryonic stem cell lines derived from human blastocysts. Science, 282(5391), 1145–1147.PubMedCrossRefGoogle Scholar
  3. 3.
    Robinton, D. A., & Daley, G. Q. (2012). The promise of induced pluripotent stem cells in research and therapy. Nature, 481(7381), 295–305. doi: 10.1038/nature10761.PubMedCrossRefGoogle Scholar
  4. 4.
    Takahashi, K., & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126(4), 663–676. doi: 10.1016/j.cell.2006.07.024.PubMedCrossRefGoogle Scholar
  5. 5.
    Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., et al. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell, 131(5), 861–872. doi: 10.1016/j.cell.2007.11.019.PubMedCrossRefGoogle Scholar
  6. 6.
    Reaven, G. M. (1988). Banting lecture 1988. Role of insulin resistance in human disease. Diabetes, 37(12), 1595–1607.PubMedCrossRefGoogle Scholar
  7. 7.
    Lakka, H. M., Laaksonen, D. E., Lakka, T. A., Niskanen, L. K., Kumpusalo, E., Tuomilehto, J., et al. (2002). The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA: The Journal of the American Medical Association, 288(21), 2709–2716.CrossRefGoogle Scholar
  8. 8.
    Haffner, S. M., Lehto, S., Ronnemaa, T., Pyorala, K., & Laakso, M. (1998). Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. The New England Journal of Medicine, 339(4), 229–234. doi: 10.1056/NEJM199807233390404.PubMedCrossRefGoogle Scholar
  9. 9.
    Malik, S., Wong, N. D., Franklin, S. S., Kamath, T. V., L’Italien, G. J., Pio, J. R., et al. (2004). Impact of the metabolic syndrome on mortality from coronary heart disease, cardiovascular disease, and all causes in United States adults. Circulation, 110(10), 1245–1250. doi: 10.1161/01.CIR.0000140677.20606.0E.PubMedCrossRefGoogle Scholar
  10. 10.
    Park, I. H., Arora, N., Huo, H., Maherali, N., Ahfeldt, T., Shimamura, A., et al. (2008). Disease-specific induced pluripotent stem cells. Cell, 134(5), 877–886. doi: 10.1016/j.cell.2008.07.041.PubMedCrossRefGoogle Scholar
  11. 11.
    Maehr, R., Chen, S., Snitow, M., Ludwig, T., Yagasaki, L., Goland, R., et al. (2009). Generation of pluripotent stem cells from patients with type 1 diabetes. Proceedings of the National Academy of Sciences of the United States of America, 106(37), 15768–15773. doi: 10.1073/pnas.0906894106.PubMedCrossRefGoogle Scholar
  12. 12.
    Murry, C. E., & Keller, G. (2008). Differentiation of embryonic stem cells to clinically relevant populations: lessons from embryonic development. Cell, 132(4), 661–680. doi: 10.1016/j.cell.2008.02.008.PubMedCrossRefGoogle Scholar
  13. 13.
    Meyer, J. S., Shearer, R. L., Capowski, E. E., Wright, L. S., Wallace, K. A., McMillan, E. L., et al. (2009). Modeling early retinal development with human embryonic and induced pluripotent stem cells. Proceedings of the National Academy of Sciences of the United States of America, 106(39), 16698–16703. doi: 10.1073/pnas.0905245106.PubMedCrossRefGoogle Scholar
  14. 14.
    Hu, B. Y., Weick, J. P., Yu, J., Ma, L. X., Zhang, X. Q., Thomson, J. A., et al. (2010). Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency. Proceedings of the National Academy of Sciences of the United States of America, 107(9), 4335–4340. doi: 10.1073/pnas.0910012107.PubMedCrossRefGoogle Scholar
  15. 15.
    Kim, K., Doi, A., Wen, B., Ng, K., Zhao, R., Cahan, P., et al. (2010). Epigenetic memory in induced pluripotent stem cells. Nature, 467(7313), 285–290. doi: 10.1038/nature09342.PubMedCrossRefGoogle Scholar
  16. 16.
    Polo, J. M., Liu, S., Figueroa, M. E., Kulalert, W., Eminli, S., Tan, K. Y., et al. (2010). Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells. Nature Biotechnology, 28(8), 848–855. doi: 10.1038/nbt.1667.PubMedCrossRefGoogle Scholar
  17. 17.
    Osafune, K., Caron, L., Borowiak, M., Martinez, R. J., Fitz-Gerald, C. S., Sato, Y., et al. (2008). Marked differences in differentiation propensity among human embryonic stem cell lines. Nature Biotechnology, 26(3), 313–315. doi: 10.1038/nbt1383.PubMedCrossRefGoogle Scholar
  18. 18.
    Nguyen, H. N., Byers, B., Cord, B., Shcheglovitov, A., Byrne, J., Gujar, P., et al. (2011). LRRK2 mutant iPSC-derived DA neurons demonstrate increased susceptibility to oxidative stress. Cell Stem Cell, 8(3), 267–280. doi: 10.1016/j.stem.2011.01.013.PubMedCrossRefGoogle Scholar
  19. 19.
    Brennand, K. J., Simone, A., Jou, J., Gelboin-Burkhart, C., Tran, N., Sangar, S., et al. (2011). Modelling schizophrenia using human induced pluripotent stem cells. Nature, 473(7346), 221–225. doi: 10.1038/nature09915.PubMedCrossRefGoogle Scholar
  20. 20.
    Cao, N., Liu, Z., Chen, Z., Wang, J., Chen, T., Zhao, X., et al. (2012). Ascorbic acid enhances the cardiac differentiation of induced pluripotent stem cells through promoting the proliferation of cardiac progenitor cells. Cell Research, 22(1), 219–236. doi: 10.1038/cr.2011.195.PubMedCrossRefGoogle Scholar
  21. 21.
    Beqqali, A., Kloots, J., Ward-van Oostwaard, D., Mummery, C., & Passier, R. (2006). Genome-wide transcriptional profiling of human embryonic stem cells differentiating to cardiomyocytes. Stem Cells, 24(8), 1956–1967. doi: 10.1634/stemcells.2006-0054.PubMedCrossRefGoogle Scholar
  22. 22.
    Davis, R. P., van den Berg, C. W., Casini, S., Braam, S. R., & Mummery, C. L. (2011). Pluripotent stem cell models of cardiac disease and their implication for drug discovery and development. Trends in Molecular Medicine, 17(9), 475–484. doi: 10.1016/j.molmed.2011.05.001.PubMedCrossRefGoogle Scholar
  23. 23.
    Itzhaki, I., Rapoport, S., Huber, I., Mizrahi, I., Zwi-Dantsis, L., Arbel, G., et al. (2011). Calcium handling in human induced pluripotent stem cell derived cardiomyocytes. PloS One, 6(4), e18037. doi: 10.1371/journal.pone.0018037.PubMedCrossRefGoogle Scholar
  24. 24.
    Qiu, C., Olivier, E. N., Velho, M., & Bouhassira, E. E. (2008). Globin switches in yolk sac-like primitive and fetal-like definitive red blood cells produced from human embryonic stem cells. Blood, 111(4), 2400–2408. doi: 10.1182/blood-2007-07-102087.PubMedCrossRefGoogle Scholar
  25. 25.
    Kroon, E., Martinson, L. A., Kadoya, K., Bang, A. G., Kelly, O. G., Eliazer, S., et al. (2008). Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo. Nature Biotechnology, 26(4), 443–452. doi: 10.1038/nbt1393.PubMedCrossRefGoogle Scholar
  26. 26.
    Park, T. S., Zimmerlin, L., & Zambidis, E. T. (2012). Efficient and simultaneous generation of hematopoietic and vascular progenitors from human induced pluripotent stem cells. Cytometry Part A: The Journal of the International Society for Analytical Cytology. doi: 10.1002/cyto.a.22090.
  27. 27.
    Li, Z., Hu, S., Ghosh, Z., Han, Z., & Wu, J. C. (2011). Functional characterization and expression profiling of human induced pluripotent stem cell- and embryonic stem cell-derived endothelial cells. Stem Cells and Development, 20(10), 1701–1710. doi: 10.1089/scd.2010.0426.PubMedCrossRefGoogle Scholar
  28. 28.
    Drukker, M., Tang, C., Ardehali, R., Rinkevich, Y., Seita, J., Lee, A. S., et al. (2012). Isolation of primitive endoderm, mesoderm, vascular endothelial and trophoblast progenitors from human pluripotent stem cells. Nature Biotechnology, 30(6), 531–542. doi: 10.1038/nbt.2239.PubMedCrossRefGoogle Scholar
  29. 29.
    Dimos, J. T., Rodolfa, K. T., Niakan, K. K., Weisenthal, L. M., Mitsumoto, H., Chung, W., et al. (2008). Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science, 321(5893), 1218–1221. doi: 10.1126/science.1158799.PubMedCrossRefGoogle Scholar
  30. 30.
    Keller, G. (2005). Embryonic stem cell differentiation: emergence of a new era in biology and medicine. Genes & Development, 19(10), 1129–1155. doi: 10.1101/gad.1303605.CrossRefGoogle Scholar
  31. 31.
    Chambers, S. M., Fasano, C. A., Papapetrou, E. P., Tomishima, M., Sadelain, M., & Studer, L. (2009). Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nature Biotechnology, 27(3), 275–280. doi: 10.1038/nbt.1529.PubMedCrossRefGoogle Scholar
  32. 32.
    Soldner, F., Hockemeyer, D., Beard, C., Gao, Q., Bell, G. W., Cook, E. G., et al. (2009). Parkinson’s disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell, 136(5), 964–977. doi: 10.1016/j.cell.2009.02.013.PubMedCrossRefGoogle Scholar
  33. 33.
    Itskovitz-Eldor, J., Schuldiner, M., Karsenti, D., Eden, A., Yanuka, O., Amit, M., et al. (2000). Differentiation of human embryonic stem cells into embryoid bodies compromising the three embryonic germ layers. Molecular Medicine, 6(2), 88–95.PubMedGoogle Scholar
  34. 34.
    Martin, G. R., & Evans, M. J. (1975). Differentiation of clonal lines of teratocarcinoma cells: formation of embryoid bodies in vitro. Proceedings of the National Academy of Sciences of the United States of America, 72(4), 1441–1445.PubMedCrossRefGoogle Scholar
  35. 35.
    Logan, C. Y., & Nusse, R. (2004). The Wnt signaling pathway in development and disease. Annual Review of Cell and Developmental Biology, 20, 781–810. doi: 10.1146/annurev.cellbio.20.010403.113126.PubMedCrossRefGoogle Scholar
  36. 36.
    Schier, A. F. (2003). Nodal signaling in vertebrate development. Annual Review of Cell and Developmental Biology, 19, 589–621. doi: 10.1146/annurev.cellbio.19.041603.094522.PubMedCrossRefGoogle Scholar
  37. 37.
    Niswander, L., & Martin, G. R. (1992). Fgf-4 expression during gastrulation, myogenesis, limb and tooth development in the mouse. Development, 114(3), 755–768.PubMedGoogle Scholar
  38. 38.
    Burridge, P. W., Keller, G., Gold, J. D., & Wu, J. C. (2012). Production of de novo cardiomyocytes: human pluripotent stem cell differentiation and direct reprogramming. Cell Stem Cell, 10(1), 16–28. doi: 10.1016/j.stem.2011.12.013.PubMedCrossRefGoogle Scholar
  39. 39.
    Willems, E., Bushway, P. J., & Mercola, M. (2009). Natural and synthetic regulators of embryonic stem cell cardiogenesis. Pediatric Cardiology, 30(5), 635–642. doi: 10.1007/s00246-009-9409-2.PubMedCrossRefGoogle Scholar
  40. 40.
    Huber, I., Itzhaki, I., Caspi, O., Arbel, G., Tzukerman, M., Gepstein, A., et al. (2007). Identification and selection of cardiomyocytes during human embryonic stem cell differentiation. FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology, 21(10), 2551–2563. doi: 10.1096/fj.05-5711com.CrossRefGoogle Scholar
  41. 41.
    Kita-Matsuo, H., Barcova, M., Prigozhina, N., Salomonis, N., Wei, K., Jacot, J. G., et al. (2009). Lentiviral vectors and protocols for creation of stable hESC lines for fluorescent tracking and drug resistance selection of cardiomyocytes. PloS One, 4(4), e5046. doi: 10.1371/journal.pone.0005046.PubMedCrossRefGoogle Scholar
  42. 42.
    Sachdev, B., Takenaka, T., Teraguchi, H., Tei, C., Lee, P., McKenna, W. J., et al. (2002). Prevalence of Anderson-Fabry disease in male patients with late onset hypertrophic cardiomyopathy. Circulation, 105(12), 1407–1411.PubMedCrossRefGoogle Scholar
  43. 43.
    Arad, M., Maron, B. J., Gorham, J. M., Johnson, W. H., Jr., Saul, J. P., Perez-Atayde, A. R., et al. (2005). Glycogen storage diseases presenting as hypertrophic cardiomyopathy. The New England Journal of Medicine, 352(4), 362–372. doi: 10.1056/NEJMoa033349.PubMedCrossRefGoogle Scholar
  44. 44.
    Van den Hout, H., Reuser, A. J., Vulto, A. G., Loonen, M. C., Cromme-Dijkhuis, A., & Van der Ploeg, A. T. (2000). Recombinant human alpha-glucosidase from rabbit milk in Pompe patients. Lancet, 356(9227), 397–398.PubMedCrossRefGoogle Scholar
  45. 45.
    Nakao, S., Takenaka, T., Maeda, M., Kodama, C., Tanaka, A., Tahara, M., et al. (1995). An atypical variant of Fabry’s disease in men with left ventricular hypertrophy. The New England Journal of Medicine, 333(5), 288–293. doi: 10.1056/NEJM199508033330504.PubMedCrossRefGoogle Scholar
  46. 46.
    Danon, M. J., Oh, S. J., DiMauro, S., Manaligod, J. R., Eastwood, A., Naidu, S., et al. (1981). Lysosomal glycogen storage disease with normal acid maltase. Neurology, 31(1), 51–57.PubMedCrossRefGoogle Scholar
  47. 47.
    Nishino, I., Fu, J., Tanji, K., Yamada, T., Shimojo, S., Koori, T., et al. (2000). Primary LAMP-2 deficiency causes X-linked vacuolar cardiomyopathy and myopathy (Danon disease). Nature, 406(6798), 906–910. doi: 10.1038/35022604.PubMedCrossRefGoogle Scholar
  48. 48.
    Rashid, S. T., Corbineau, S., Hannan, N., Marciniak, S. J., Miranda, E., Alexander, G., et al. (2010). Modeling inherited metabolic disorders of the liver using human induced pluripotent stem cells. The Journal of Clinical Investigation, 120(9), 3127–3136. doi: 10.1172/JCI43122.PubMedCrossRefGoogle Scholar
  49. 49.
    Bernier, A. V., Correia, C. E., Haller, M. J., Theriaque, D. W., Shuster, J. J., & Weinstein, D. A. (2009). Vascular dysfunction in glycogen storage disease type I. The Journal of Pediatrics, 154(4), 588–591. doi: 10.1016/j.jpeds.2008.10.048.PubMedCrossRefGoogle Scholar
  50. 50.
    Lee, P. J., Celermajer, D. S., Robinson, J., McCarthy, S. N., Betteridge, D. J., & Leonard, J. V. (1994). Hyperlipidaemia does not impair vascular endothelial function in glycogen storage disease type 1a. Atherosclerosis, 110(1), 95–100.PubMedCrossRefGoogle Scholar
  51. 51.
    Kawagoe, S., Higuchi, T., Meng, X. L., Shimada, Y., Shimizu, H., Hirayama, R., et al. (2011). Generation of induced pluripotent stem (iPS) cells derived from a murine model of Pompe disease and differentiation of Pompe-iPS cells into skeletal muscle cells. Molecular Genetics and Metabolism, 104(1–2), 123–128. doi: 10.1016/j.ymgme.2011.05.020.PubMedCrossRefGoogle Scholar
  52. 52.
    Luptak, I., Shen, M., He, H., Hirshman, M. F., Musi, N., Goodyear, L. J., et al. (2007). Aberrant activation of AMP-activated protein kinase remodels metabolic network in favor of cardiac glycogen storage. The Journal of Clinical Investigation, 117(5), 1432–1439. doi: 10.1172/JCI30658.PubMedCrossRefGoogle Scholar
  53. 53.
    Arad, M., Seidman, C. E., & Seidman, J. G. (2007). AMP-activated protein kinase in the heart: role during health and disease. Circulation Research, 100(4), 474–488. doi: 10.1161/01.RES.0000258446.23525.37.PubMedCrossRefGoogle Scholar
  54. 54.
    Kahn, B. B., Alquier, T., Carling, D., & Hardie, D. G. (2005). AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metabolism, 1(1), 15–25. doi: 10.1016/j.cmet.2004.12.003.PubMedCrossRefGoogle Scholar
  55. 55.
    Schweiger, M., Lass, A., Zimmermann, R., Eichmann, T. O., & Zechner, R. (2009). Neutral lipid storage disease: genetic disorders caused by mutations in adipose triglyceride lipase/PNPLA2 or CGI-58/ABHD5. American Journal of Physiology, Endocrinology and Metabolism, 297(2), E289–E296. doi: 10.1152/ajpendo.00099.2009.CrossRefGoogle Scholar
  56. 56.
    Chanarin, I., Patel, A., Slavin, G., Wills, E. J., Andrews, T. M., & Stewart, G. (1975). Neutral-lipid storage disease: a new disorder of lipid metabolism. British Medical Journal, 1(5957), 553–555.PubMedCrossRefGoogle Scholar
  57. 57.
    Dorfman, M. L., Hershko, C., Eisenberg, S., & Sagher, F. (1974). Ichthyosiform dermatosis with systemic lipidosis. Archives of Dermatology, 110(2), 261–266.PubMedCrossRefGoogle Scholar
  58. 58.
    Igal, R. A., Rhoads, J. M., & Coleman, R. A. (1997). Neutral lipid storage disease with fatty liver and cholestasis. Journal of Pediatric Gastroenterology and Nutrition, 25(5), 541–547.PubMedCrossRefGoogle Scholar
  59. 59.
    Lefevre, C., Jobard, F., Caux, F., Bouadjar, B., Karaduman, A., Heilig, R., et al. (2001). Mutations in CGI-58, the gene encoding a new protein of the esterase/lipase/thioesterase subfamily, in Chanarin-Dorfman syndrome. American Journal of Human Genetics, 69(5), 1002–1012. doi: 10.1086/324121.PubMedCrossRefGoogle Scholar
  60. 60.
    Lass, A., Zimmermann, R., Haemmerle, G., Riederer, M., Schoiswohl, G., Schweiger, M., et al. (2006). Adipose triglyceride lipase-mediated lipolysis of cellular fat stores is activated by CGI-58 and defective in Chanarin-Dorfman Syndrome. Cell Metabolism, 3(5), 309–319. doi: 10.1016/j.cmet.2006.03.005.PubMedCrossRefGoogle Scholar
  61. 61.
    Zimmermann, R., Strauss, J. G., Haemmerle, G., Schoiswohl, G., Birner-Gruenberger, R., Riederer, M., et al. (2004). Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase. Science, 306(5700), 1383–1386. doi: 10.1126/science.1100747.PubMedCrossRefGoogle Scholar
  62. 62.
    Villena, J. A., Roy, S., Sarkadi-Nagy, E., Kim, K. H., & Sul, H. S. (2004). Desnutrin, an adipocyte gene encoding a novel patatin domain-containing protein, is induced by fasting and glucocorticoids: ectopic expression of desnutrin increases triglyceride hydrolysis. The Journal of Biological Chemistry, 279(45), 47066–47075. doi: 10.1074/jbc.M403855200.PubMedCrossRefGoogle Scholar
  63. 63.
    Jenkins, C. M., Mancuso, D. J., Yan, W., Sims, H. F., Gibson, B., & Gross, R. W. (2004). Identification, cloning, expression, and purification of three novel human calcium-independent phospholipase A2 family members possessing triacylglycerol lipase and acylglycerol transacylase activities. The Journal of Biological Chemistry, 279(47), 48968–48975. doi: 10.1074/jbc.M407841200.PubMedCrossRefGoogle Scholar
  64. 64.
    Kershaw, E. E., Hamm, J. K., Verhagen, L. A., Peroni, O., Katic, M., & Flier, J. S. (2006). Adipose triglyceride lipase: function, regulation by insulin, and comparison with adiponutrin. Diabetes, 55(1), 148–157.PubMedCrossRefGoogle Scholar
  65. 65.
    Haemmerle, G., Lass, A., Zimmermann, R., Gorkiewicz, G., Meyer, C., Rozman, J., et al. (2006). Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase. Science, 312(5774), 734–737. doi: 10.1126/science.1123965.PubMedCrossRefGoogle Scholar
  66. 66.
    Hirano, K., Ikeda, Y., Zaima, N., Sakata, Y., & Matsumiya, G. (2008). Triglyceride deposit cardiomyovasculopathy. The New England Journal of Medicine, 359(22), 2396–2398. doi: 10.1056/NEJMc0805305.PubMedCrossRefGoogle Scholar
  67. 67.
    Fischer, J., Lefevre, C., Morava, E., Mussini, J. M., Laforet, P., Negre-Salvayre, A., et al. (2007). The gene encoding adipose triglyceride lipase (PNPLA2) is mutated in neutral lipid storage disease with myopathy. Nature Genetics, 39(1), 28–30. doi: 10.1038/ng1951.PubMedCrossRefGoogle Scholar
  68. 68.
    Lake, A. C., Sun, Y., Li, J. L., Kim, J. E., Johnson, J. W., Li, D., et al. (2005). Expression, regulation, and triglyceride hydrolase activity of adiponutrin family members. Journal of Lipid Research, 46(11), 2477–2487. doi: 10.1194/jlr.M500290-JLR200.PubMedCrossRefGoogle Scholar
  69. 69.
    Pinent, M., Hackl, H., Burkard, T. R., Prokesch, A., Papak, C., Scheideler, M., et al. (2008). Differential transcriptional modulation of biological processes in adipocyte triglyceride lipase and hormone-sensitive lipase-deficient mice. Genomics, 92(1), 26–32. doi: 10.1016/j.ygeno.2008.03.010.PubMedCrossRefGoogle Scholar
  70. 70.
    Kobayashi, K., Inoguchi, T., Maeda, Y., Nakashima, N., Kuwano, A., Eto, E., et al. (2008). The lack of the C-terminal domain of adipose triglyceride lipase causes neutral lipid storage disease through impaired interactions with lipid droplets. The Journal of Clinical Endocrinology and Metabolism, 93(7), 2877–2884. doi: 10.1210/jc.2007-2247.PubMedCrossRefGoogle Scholar
  71. 71.
    Hanna, J., Wernig, M., Markoulaki, S., Sun, C. W., Meissner, A., Cassady, J. P., et al. (2007). Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science, 318(5858), 1920–1923. doi: 10.1126/science.1152092.PubMedCrossRefGoogle Scholar
  72. 72.
    Yusa, K., Rashid, S. T., Strick-Marchand, H., Varela, I., Liu, P. Q., Paschon, D. E., et al. (2011). Targeted gene correction of alpha1-antitrypsin deficiency in induced pluripotent stem cells. Nature, 478(7369), 391–394. doi: 10.1038/nature10424.PubMedCrossRefGoogle Scholar
  73. 73.
    Hockemeyer, D., Soldner, F., Beard, C., Gao, Q., Mitalipova, M., DeKelver, R. C., et al. (2009). Efficient targeting of expressed and silent genes in human ESCs and iPSCs using zinc-finger nucleases. Nature Biotechnology, 27(9), 851–857. doi: 10.1038/nbt.1562.PubMedCrossRefGoogle Scholar
  74. 74.
    Lombardo, A., Genovese, P., Beausejour, C. M., Colleoni, S., Lee, Y. L., Kim, K. A., et al. (2007). Gene editing in human stem cells using zinc finger nucleases and integrase-defective lentiviral vector delivery. Nature Biotechnology, 25(11), 1298–1306. doi: 10.1038/nbt1353.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  1. 1.Department of Medicine, Massachusetts General HospitalHarvard Medical SchoolBostonUSA
  2. 2.Department of Cardiovascular Medicine, Graduate School of MedicineOsaka UniversityOsakaJapan
  3. 3.Cardiovascular Research Center, Division of Cardiology, Department of Medicine, Massachusetts General HospitalHarvard Medical SchoolBostonUSA
  4. 4.Harvard Stem Cell InstituteCambridgeUSA
  5. 5.Massachusetts General HospitalBostonUSA
  6. 6.Massachusetts General HospitalBostonUSA
  7. 7.Stanford UniversityStanfordUSA

Personalised recommendations