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Patient-derived induced pluripotent stem cells in cancer research and precision oncology

An Author Correction to this article was published on 03 April 2019

Abstract

Together with recent advances in the processing and culture of human tissue, bioengineering, xenotransplantation and genome editing, Induced pluripotent stem cells (iPSCs) present a range of new opportunities for the study of human cancer. Here we discuss the main advantages and limitations of iPSC modeling, and how the method intersects with other patient-derived models of cancer, such as organoids, organs-on-chips and patient-derived xenografts (PDXs). We highlight the opportunities that iPSC models can provide beyond those offered by existing systems and animal models and present current challenges and crucial areas for future improvements toward wider adoption of this technology.

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Figure 1: An overview of iPSCs and cancer modeling.

Marina Corral Spence/Springer Nature

Figure 2: Potential uses of iPSCs in basic cancer research.

Marina Corral Spence/Springer Nature

Figure 3: Applications of iPSCs in translational cancer research.

Marina Corral Spence/Springer Nature

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References

  1. Takahashi, K. & Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663–676 (2006).

    Article  CAS  PubMed  Google Scholar 

  2. Takahashi, K. et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861–872 (2007).

    Article  CAS  PubMed  Google Scholar 

  3. Papapetrou, E.P. Induced pluripotent stem cells, past and future. Science 353, 991–992 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Onder, T.T. & Daley, G.Q. New lessons learned from disease modeling with induced pluripotent stem cells. Curr. Opin. Genet. Dev. 22, 500–508 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Zeltner, N. & Studer, L. Pluripotent stem cell-based disease modeling: current hurdles and future promise. Curr. Opin. Cell Biol. 37, 102–110 (2015).

    Article  CAS  PubMed  Google Scholar 

  6. Liu, X. et al. ROCK inhibitor and feeder cells induce the conditional reprogramming of epithelial cells. Am. J. Pathol. 180, 599–607 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Crystal, A.S. et al. Patient-derived models of acquired resistance can identify effective drug combinations for cancer. Science 346, 1480–1486 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Sachs, N. & Clevers, H. Organoid cultures for the analysis of cancer phenotypes. Curr. Opin. Genet. Dev. 24, 68–73 (2014).

    Article  CAS  PubMed  Google Scholar 

  9. Fatehullah, A., Tan, S.H. & Barker, N. Organoids as an in vitro model of human development and disease. Nat. Cell Biol. 18, 246–254 (2016).

    Article  PubMed  CAS  Google Scholar 

  10. Ridky, T.W., Chow, J.M., Wong, D.J. & Khavari, P.A. Invasive three-dimensional organotypic neoplasia from multiple normal human epithelia. Nat. Med. 16, 1450–1455 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Vaira, V. et al. Preclinical model of organotypic culture for pharmacodynamic profiling of human tumors. Proc. Natl. Acad. Sci. USA 107, 8352–8356 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Majumder, B. et al. Predicting clinical response to anticancer drugs using an ex vivo platform that captures tumour heterogeneity. Nat. Commun. 6, 6169 (2015).

    Article  CAS  PubMed  Google Scholar 

  13. Gould, S.E., Junttila, M.R. & de Sauvage, F.J. Translational value of mouse models in oncology drug development. Nat. Med. 21, 431–439 (2015).

    Article  CAS  PubMed  Google Scholar 

  14. Day, C.P., Merlino, G. & Van Dyke, T. Preclinical mouse cancer models: a maze of opportunities and challenges. Cell 163, 39–53 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ingber, D.E. Reverse engineering human pathophysiology with organs-on-chips. Cell 164, 1105–1109 (2016).

    Article  CAS  PubMed  Google Scholar 

  16. Hochedlinger, K. et al. Reprogramming of a melanoma genome by nuclear transplantation. Genes Dev. 18, 1875–1885 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Blelloch, R.H. et al. Nuclear cloning of embryonal carcinoma cells. Proc. Natl. Acad. Sci. USA 101, 13985–13990 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Carette, J.E. et al. Generation of iPSCs from cultured human malignant cells. Blood 115, 4039–4042 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Utikal, J., Maherali, N., Kulalert, W. & Hochedlinger, K. Sox2 is dispensable for the reprogramming of melanocytes and melanoma cells into induced pluripotent stem cells. J. Cell Sci. 122, 3502–3510 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Miyoshi, N. et al. Defined factors induce reprogramming of gastrointestinal cancer cells. Proc. Natl. Acad. Sci. USA 107, 40–45 (2010).

    Article  CAS  PubMed  Google Scholar 

  21. Zhang, X., Cruz, F.D., Terry, M., Remotti, F. & Matushansky, I. Terminal differentiation and loss of tumorigenicity of human cancers via pluripotency-based reprogramming. Oncogene 32, 2249–2260 (2013).

    Article  CAS  PubMed  Google Scholar 

  22. Stricker, S.H. et al. Widespread resetting of DNA methylation in glioblastoma-initiating cells suppresses malignant cellular behavior in a lineage-dependent manner. Genes Dev. 27, 654–669 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Corominas-Faja, B. et al. Nuclear reprogramming of luminal-like breast cancer cells generates Sox2-overexpressing cancer stem-like cellular states harboring transcriptional activation of the mTOR pathway. Cell Cycle 12, 3109–3124 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kim, J. & Zaret, K.S. Reprogramming of human cancer cells to pluripotency for models of cancer progression. EMBO J. 34, 739–747 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Hu, K. et al. Efficient generation of transgene-free induced pluripotent stem cells from normal and neoplastic bone marrow and cord blood mononuclear cells. Blood 117, e109–e119 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Gandre-Babbe, S. et al. Patient-derived induced pluripotent stem cells recapitulate hematopoietic abnormalities of juvenile myelomonocytic leukemia. Blood 121, 4925–4929 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kumano, K. et al. Generation of induced pluripotent stem cells from primary chronic myelogenous leukemia patient samples. Blood 119, 6234–6242 (2012).

    Article  CAS  PubMed  Google Scholar 

  28. Hosoi, M. et al. Generation of induced pluripotent stem cells derived from primary and secondary myelofibrosis patient samples. Exp. Hematol. 42, 816–825 (2014).

    Article  CAS  PubMed  Google Scholar 

  29. Kotini, A.G. et al. Functional analysis of a chromosomal deletion associated with myelodysplastic syndromes using isogenic human induced pluripotent stem cells. Nat. Biotechnol. 33, 646–655 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Ye, Z. et al. Human-induced pluripotent stem cells from blood cells of healthy donors and patients with acquired blood disorders. Blood 114, 5473–5480 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Ye, Z. et al. Differential sensitivity to JAK inhibitory drugs by isogenic human erythroblasts and hematopoietic progenitors generated from patient-specific induced pluripotent stem cells. Stem Cells 32, 269–278 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Mulero-Navarro, S. et al. Myeloid dysregulation in a human induced pluripotent stem cell model of PTPN11-associated juvenile myelomonocytic leukemia. Cell Rep. 13, 504–515 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Kim, J. et al. An iPSC line from human pancreatic ductal adenocarcinoma undergoes early to invasive stages of pancreatic cancer progression. Cell Rep. 3, 2088–2099 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Lee, D.F. et al. Modeling familial cancer with induced pluripotent stem cells. Cell 161, 240–254 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Müller, L.U. et al. Overcoming reprogramming resistance of Fanconi anemia cells. Blood 119, 5449–5457 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Antony-Debré, I. et al. Level of RUNX1 activity is critical for leukemic predisposition but not for thrombocytopenia. Blood 125, 930–940 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Soyombo, A.A. et al. Analysis of induced pluripotent stem cells from a BRCA1 mutant family. Stem Cell Reports 1, 336–349 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Takahashi, K. & Yamanaka, S. A decade of transcription factor-mediated reprogramming to pluripotency. Nat. Rev. Mol. Cell Biol. 17, 183–193 (2016).

    Article  CAS  PubMed  Google Scholar 

  39. Apostolou, E. & Hochedlinger, K. Chromatin dynamics during cellular reprogramming. Nature 502, 462–471 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Jaenisch, R. & Young, R. Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming. Cell 132, 567–582 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Papapetrou, E.P. et al. Stoichiometric and temporal requirements of Oct4, Sox2, Klf4, and c-Myc expression for efficient human iPSC induction and differentiation. Proc. Natl. Acad. Sci. USA 106, 12759–12764 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Wernig, M. et al. In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature 448, 318–324 (2007).

    Article  CAS  PubMed  Google Scholar 

  43. Chin, M.H., Pellegrini, M., Plath, K. & Lowry, W.E. Molecular analyses of human induced pluripotent stem cells and embryonic stem cells. Cell Stem Cell 7, 263–269 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Tapia, N. & Schöler, H.R. Molecular obstacles to clinical translation of iPSCs. Cell Stem Cell 19, 298–309 (2016).

    Article  CAS  PubMed  Google Scholar 

  45. Krijger, P.H. et al. Cell-of-origin-specific 3D genome structure acquired during somatic cell reprogramming. Cell Stem Cell 18, 597–610 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. De Los Angeles, A. et al. Hallmarks of pluripotency. Nature 525, 469–478 (2015).

    Article  CAS  PubMed  Google Scholar 

  47. Chen, K.G., Mallon, B.S., McKay, R.D. & Robey, P.G. Human pluripotent stem cell culture: considerations for maintenance, expansion, and therapeutics. Cell Stem Cell 14, 13–26 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Rouhani, F. et al. Genetic background drives transcriptional variation in human induced pluripotent stem cells. PLoS Genet. 10, e1004432 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Kyttälä, A. et al. Genetic variability overrides the impact of parental cell type and determines iPSC differentiation potential. Stem Cell Reports 6, 200–212 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  50. Féraud, O. et al. Donor dependent variations in hematopoietic differentiation among embryonic and induced pluripotent stem cell lines. PLoS One 11, e0149291 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Burrows, C.K. et al. Genetic variation, not cell type of origin, underlies the majority of identifiable regulatory differences in iPSCs. PLoS Genet. 12, e1005793 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Utikal, J. et al. Immortalization eliminates a roadblock during cellular reprogramming into iPS cells. Nature 460, 1145–1148 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Marión, R.M. et al. A p53-mediated DNA damage response limits reprogramming to ensure iPS cell genomic integrity. Nature 460, 1149–1153 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Kawamura, T. et al. Linking the p53 tumour suppressor pathway to somatic cell reprogramming. Nature 460, 1140–1144 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Li, H. et al. The Ink4/Arf locus is a barrier for iPS cell reprogramming. Nature 460, 1136–1139 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Raya, A. et al. Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells. Nature 460, 53–59 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Hanna, J. et al. Direct cell reprogramming is a stochastic process amenable to acceleration. Nature 462, 595–601 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Ruiz, S. et al. A high proliferation rate is required for cell reprogramming and maintenance of human embryonic stem cell identity. Curr. Biol. 21, 45–52 (2011).

    Article  CAS  PubMed  Google Scholar 

  59. Guo, S. et al. Nonstochastic reprogramming from a privileged somatic cell state. Cell 156, 649–662 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Papapetrou, E.P. & Sadelain, M. Generation of transgene-free human induced pluripotent stem cells with an excisable single polycistronic vector. Nat. Protoc. 6, 1251–1273 (2011).

    Article  CAS  PubMed  Google Scholar 

  61. Visvader, J.E. Cells of origin in cancer. Nature 469, 314–322 (2011).

    Article  CAS  PubMed  Google Scholar 

  62. Chen, Y. et al. Engineering human stem cell lines with inducible gene knockout using CRISPR/Cas9. Cell Stem Cell 17, 233–244 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Hrvatin, S. et al. Differentiated human stem cells resemble fetal, not adult, β cells. Proc. Natl. Acad. Sci. USA 111, 3038–3043 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. van den Berg, C.W. et al. Transcriptome of human foetal heart compared with cardiomyocytes from pluripotent stem cells. Development 142, 3231–3238 (2015).

    Article  CAS  PubMed  Google Scholar 

  65. Rowe, R.G., Mandelbaum, J., Zon, L.I. & Daley, G.Q. Engineering hematopoietic stem cells: lessons from development. Cell Stem Cell 18, 707–720 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Hussein, S.M. et al. Copy number variation and selection during reprogramming to pluripotency. Nature 471, 58–62 (2011).

    Article  CAS  PubMed  Google Scholar 

  67. Ji, J. et al. Elevated coding mutation rate during the reprogramming of human somatic cells into induced pluripotent stem cells. Stem Cells 30, 435–440 (2012).

    Article  CAS  PubMed  Google Scholar 

  68. Young, M.A. et al. Background mutations in parental cells account for most of the genetic heterogeneity of induced pluripotent stem cells. Cell Stem Cell 10, 570–582 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Abyzov, A. et al. Somatic copy number mosaicism in human skin revealed by induced pluripotent stem cells. Nature 492, 438–442 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Cheng, L. et al. Low incidence of DNA sequence variation in human induced pluripotent stem cells generated by nonintegrating plasmid expression. Cell Stem Cell 10, 337–344 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Mayshar, Y. et al. Identification and classification of chromosomal aberrations in human induced pluripotent stem cells. Cell Stem Cell 7, 521–531 (2010).

    Article  CAS  PubMed  Google Scholar 

  72. Laurent, L.C. et al. Dynamic changes in the copy number of pluripotency and cell proliferation genes in human ESCs and iPSCs during reprogramming and time in culture. Cell Stem Cell 8, 106–118 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Varela, C. et al. Recurrent genomic instability of chromosome 1q in neural derivatives of human embryonic stem cells. J. Clin. Invest. 122, 569–574 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Peterson, S.E. & Loring, J.F. Genomic instability in pluripotent stem cells: implications for clinical applications. J. Biol. Chem. 289, 4578–4584 (2014).

    Article  CAS  PubMed  Google Scholar 

  75. Liang, G. & Zhang, Y. Genetic and epigenetic variations in iPSCs: potential causes and implications for application. Cell Stem Cell 13, 149–159 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Polo, J.M. et al. A molecular roadmap of reprogramming somatic cells into iPS cells. Cell 151, 1617–1632 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Papp, B. & Plath, K. Epigenetics of reprogramming to induced pluripotency. Cell 152, 1324–1343 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Kim, K. et al. Epigenetic memory in induced pluripotent stem cells. Nature 467, 285–290 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Polo, J.M. et al. Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells. Nat. Biotechnol. 28, 848–855 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Ghosh, Z. et al. Persistent donor cell gene expression among human induced pluripotent stem cells contributes to differences with human embryonic stem cells. PLoS One 5, e8975 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Bock, C. et al. Reference maps of human ES and iPS cell variation enable high-throughput characterization of pluripotent cell lines. Cell 144, 439–452 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Guenther, M.G. et al. Chromatin structure and gene expression programs of human embryonic and induced pluripotent stem cells. Cell Stem Cell 7, 249–257 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Choi, J. et al. A comparison of genetically matched cell lines reveals the equivalence of human iPSCs and ESCs. Nat. Biotechnol. 33, 1173–1181 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Hockemeyer, D. & Jaenisch, R. Induced pluripotent stem cells meet genome editing. Cell Stem Cell 18, 573–586 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Sterneckert, J.L., Reinhardt, P. & Schöler, H.R. Investigating human disease using stem cell models. Nat. Rev. Genet. 15, 625–639 (2014).

    Article  CAS  PubMed  Google Scholar 

  86. Cox, D.B., Platt, R.J. & Zhang, F. Therapeutic genome editing: prospects and challenges. Nat. Med. 21, 121–131 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Maddalo, D. et al. In vivo engineering of oncogenic chromosomal rearrangements with the CRISPR/Cas9 system. Nature 516, 423–427 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Mandegar, M.A. et al. CRISPR interference efficiently induces specific and reversible gene silencing in human iPSCs. Cell Stem Cell 18, 541–553 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Kreso, A. & Dick, J.E. Evolution of the cancer stem cell model. Cell Stem Cell 14, 275–291 (2014).

    Article  CAS  PubMed  Google Scholar 

  90. Soldner, F. et al. Parkinson-associated risk variant in distal enhancer of α-synuclein modulates target gene expression. Nature 533, 95–99 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Engle, S.J. & Puppala, D. Integrating human pluripotent stem cells into drug development. Cell Stem Cell 12, 669–677 (2013).

    Article  CAS  PubMed  Google Scholar 

  92. Engle, S.J. & Vincent, F. Small molecule screening in human induced pluripotent stem cell-derived terminal cell types. J. Biol. Chem. 289, 4562–4570 (2014).

    Article  CAS  PubMed  Google Scholar 

  93. Lee, G. et al. Large-scale screening using familial dysautonomia induced pluripotent stem cells identifies compounds that rescue IKBKAP expression. Nat. Biotechnol. 30, 1244–1248 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Wainger, B.J. et al. Intrinsic membrane hyperexcitability of amyotrophic lateral sclerosis patient-derived motor neurons. Cell Rep. 7, 1–11 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Naryshkin, N.A. et al. Motor neuron disease. SMN2 splicing modifiers improve motor function and longevity in mice with spinal muscular atrophy. Science 345, 688–693 (2014).

    Article  CAS  PubMed  Google Scholar 

  96. Ogawa, M. et al. Directed differentiation of cholangiocytes from human pluripotent stem cells. Nat. Biotechnol. 33, 853–861 (2015).

    Article  CAS  PubMed  Google Scholar 

  97. Sampaziotis, F. et al. Cholangiocytes derived from human induced pluripotent stem cells for disease modeling and drug validation. Nat. Biotechnol. 33, 845–852 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Takebe, T. et al. Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature 499, 481–484 (2013).

    Article  CAS  PubMed  Google Scholar 

  99. Takasato, M. et al. Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis. Nature 526, 564–568 (2015).

    Article  CAS  PubMed  Google Scholar 

  100. Morizane, R. et al. Nephron organoids derived from human pluripotent stem cells model kidney development and injury. Nat. Biotechnol. 33, 1193–1200 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Grskovic, M., Javaherian, A., Strulovici, B. & Daley, G.Q. Induced pluripotent stem cells--opportunities for disease modelling and drug discovery. Nat. Rev. Drug Discov. 10, 915–929 (2011).

    Article  CAS  PubMed  Google Scholar 

  102. McCracken, K.W. et al. Modelling human development and disease in pluripotent stem-cell-derived gastric organoids. Nature 516, 400–404 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Watson, C.L. et al. An in vivo model of human small intestine using pluripotent stem cells. Nat. Med. 20, 1310–1314 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Dye, B.R. et al. In vitro generation of human pluripotent stem cell derived lung organoids. eLife 4, e05098 (2015).

    Article  PubMed Central  Google Scholar 

  105. Schwartz, M.P. et al. Human pluripotent stem cell-derived neural constructs for predicting neural toxicity. Proc. Natl. Acad. Sci. USA 112, 12516–12521 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Burridge, P.W. et al. Human induced pluripotent stem cell-derived cardiomyocytes recapitulate the predilection of breast cancer patients to doxorubicin-induced cardiotoxicity. Nat. Med. 22, 547–556 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Eggert, U.S. The why and how of phenotypic small-molecule screens. Nat. Chem. Biol. 9, 206–209 (2013).

    Article  CAS  PubMed  Google Scholar 

  108. Friedman, A.A., Letai, A., Fisher, D.E. & Flaherty, K.T. Precision medicine for cancer with next-generation functional diagnostics. Nat. Rev. Cancer 15, 747–756 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Mertens, J. et al. Differential responses to lithium in hyperexcitable neurons from patients with bipolar disorder. Nature 527, 95–99 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Garbes, L. et al. VPA response in SMA is suppressed by the fatty acid translocase CD36. Hum. Mol. Genet. 22, 398–407 (2013).

    Article  CAS  PubMed  Google Scholar 

  111. Cao, L. et al. Pharmacological reversal of a pain phenotype in iPSC-derived sensory neurons and patients with inherited erythromelalgia. Sci. Transl. Med. 8, 335ra56 (2016).

    Article  PubMed  CAS  Google Scholar 

  112. Terrenoire, C. et al. Induced pluripotent stem cells used to reveal drug actions in a long QT syndrome family with complex genetics. J. Gen. Physiol. 141, 61–72 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Maqsood, M.I., Matin, M.M., Bahrami, A.R. & Ghasroldasht, M.M. Immortality of cell lines: challenges and advantages of establishment. Cell Biol. Int. 37, 1038–1045 (2013).

    Article  PubMed  Google Scholar 

  114. Elenbaas, B. et al. Human breast cancer cells generated by oncogenic transformation of primary mammary epithelial cells. Genes Dev. 15, 50–65 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Henderson, E., Miller, G., Robinson, J. & Heston, L. Efficiency of transformation of lymphocytes by Epstein-Barr virus. Virology 76, 152–163 (1977).

    Article  CAS  PubMed  Google Scholar 

  116. Maherali, N. & Hochedlinger, K. Guidelines and techniques for the generation of induced pluripotent stem cells. Cell Stem Cell 3, 595–605 (2008).

    Article  CAS  PubMed  Google Scholar 

  117. Suprynowicz, F.A. et al. Conditionally reprogrammed cells represent a stem-like state of adult epithelial cells. Proc. Natl. Acad. Sci. USA 109, 20035–20040 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Lancaster, M.A. & Knoblich, J.A. Organogenesis in a dish: modeling development and disease using organoid technologies. Science 345, 1247125 (2014).

    Article  PubMed  CAS  Google Scholar 

  119. Clevers, H. Modeling development and disease with organoids. Cell 165, 1586–1597 (2016).

    Article  CAS  PubMed  Google Scholar 

  120. Wu, J. & Izpisua Belmonte, J.C. Stem cells: a renaissance in human biology research. Cell 165, 1572–1585 (2016).

    Article  CAS  PubMed  Google Scholar 

  121. Boj, S.F. et al. Organoid models of human and mouse ductal pancreatic cancer. Cell 160, 324–338 (2015).

    Article  CAS  PubMed  Google Scholar 

  122. Huang, L. et al. Ductal pancreatic cancer modeling and drug screening using human pluripotent stem cell- and patient-derived tumor organoids. Nat. Med. 21, 1364–1371 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Sato, T. et al. Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett's epithelium. Gastroenterology 141, 1762–1772 (2011).

    Article  CAS  PubMed  Google Scholar 

  124. Gao, D. et al. Organoid cultures derived from patients with advanced prostate cancer. Cell 159, 176–187 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. van de Wetering, M. et al. Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell 161, 933–945 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Passier, R., Orlova, V. & Mummery, C. Complex tissue and disease modeling using hiPSCs. Cell Stem Cell 18, 309–321 (2016).

    Article  CAS  PubMed  Google Scholar 

  127. Guye, P. et al. Genetically engineering self-organization of human pluripotent stem cells into a liver bud-like tissue using Gata6. Nat. Commun. 7, 10243 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Giobbe, G.G. et al. Functional differentiation of human pluripotent stem cells on a chip. Nat. Methods 12, 637–640 (2015).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

E.P.P. is supported by US National Institutes of Health (NIH) grants R00 DK087923 and R01 HL121570; by the Lawrence Ellison Foundation; by the Damon Runyon Cancer Research Foundation; by the Edward Evans Foundation; and by the Taub Foundation for MDS research.

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Correspondence to Eirini P Papapetrou.

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Papapetrou, E. Patient-derived induced pluripotent stem cells in cancer research and precision oncology. Nat Med 22, 1392–1401 (2016). https://doi.org/10.1038/nm.4238

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