Skip to main content
SpringerLink
Log in

Nonintegrating Human Somatic Cell Reprogramming Methods

  • Chapter
  • First Online:
Engineering and Application of Pluripotent Stem Cells

Part of the book series: Advances in Biochemical Engineering/Biotechnology ((ABE,volume 163))

Abstract

Traditional biomedical research and preclinical studies frequently rely on animal models and repeatedly draw on a relatively small set of human cell lines, such as HeLa, HEK293, HepG2, HL60, and PANC1 cells. However, animal models often fail to reproduce important clinical phenotypes and conventional cell lines only represent a small number of cell types or diseases, have very limited ethnic/genetic diversity, and either senesce quickly or carry potentially confounding immortalizing mutations. In recent years, human pluripotent stem cells have attracted a lot of attention, in part because these cells promise more precise modeling of human diseases. Expectations are also high that pluripotent stem cell technologies can deliver cell-based therapeutics for the cure of a wide range of degenerative and other diseases. This review focuses on episomal and Sendai viral reprogramming modalities, which are the most popular methods for generating transgene-free human induced pluripotent stem cells (hiPSCs) from easily accessible cell sources.

Graphical Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

Abbreviations

cGMP:

current Good Manufacturing Practice

ECC:

Embryonal carcinoma cell

Epi:

Episomal

ESC:

Embryonic stem cell

hESC:

Human embryonic stem cell

hiPSC:

Human induced pluripotent stem cell

mESC:

Mouse embryonic stem cell

OSKM:

Oct4/Sox2/Klf4/c-Myc

PBMC:

Peripheral blood mononuclear cell

SeV:

Sendai virus/Sendai viral

TAD:

Trans-activating domain

References

  1. Birch S, Tyson E (1683) An extract of two letters from Mr. Sampson birch, an alderman and apothecary at stafford, concerning an extraordinary birth in Staffordshire, with reflections thereon by Edw. Tyson M. D. fellow of the coll. of physitians, and of the R. society. Philos Trans 13:281–284

    Article  Google Scholar 

  2. Virchow R (1863) Die krankhaften Geschwülste. Hirschwald

    Google Scholar 

  3. Kleinsmith LJ, Pierce Jr GB (1964) Multipotentiality of single embryonal carcinoma cells. Cancer Res 24:1544–1551

    CAS  Google Scholar 

  4. Martin GR, Evans MJ (1975) Differentiation of clonal lines of teratocarcinoma cells: formation of embryoid bodies in vitro. Proc Natl Acad Sci U S A 72:1441–1445

    Article  CAS  Google Scholar 

  5. Papaioannou VE, Gardner RL, McBurney MW, Babinet C, Evans MJ (1978) Participation of cultured teratocarcinoma cells in mouse embryogenesis. J Embryol Exp Morphol 44:93–104

    CAS  Google Scholar 

  6. Rossant J, McBurney MW (1982) The developmental potential of a euploid male teratocarcinoma cell line after blastocyst injection. J Embryol Exp Morphol 70:99–112

    CAS  Google Scholar 

  7. Papaioannou VE, McBurney MW, Gardner RL, Evans MJ (1975) Fate of teratocarcinoma cells injected into early mouse embryos. Nature 258:70–73

    Article  CAS  Google Scholar 

  8. Brinster RL (1974) The effect of cells transferred into the mouse blastocyst on subsequent development. J Exp Med 140:1049–1056

    Article  CAS  Google Scholar 

  9. Askanazy M (1907) Die Teratome nach ihrem Bau, ihrem Verlauf, ihrer Genese und im Vergleich zum experimentellen Teratoid. Verh Deutsch Pathol Gesellsch 11:39–82

    Google Scholar 

  10. Stevens LC (1970) The development of transplantable teratocarcinomas from intratesticular grafts of pre- and postimplantation mouse embryos. Dev Biol 21:364–382

    Article  CAS  Google Scholar 

  11. Solter D, Skreb N, Damjanov I (1970) Extrauterine growth of mouse egg-cylinders results in malignant teratoma. Nature 227:503–504

    Article  CAS  Google Scholar 

  12. Evans MJ, Kaufman MH (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292:154–156

    Article  CAS  Google Scholar 

  13. Martin GR (1981) Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci U S A 78:7634–7638

    Article  CAS  Google Scholar 

  14. Bradley A, Evans M, Kaufman MH, Robertson E (1984) Formation of germ-line chimaeras from embryo-derived teratocarcinoma cell lines. Nature 309:255–256

    Article  CAS  Google Scholar 

  15. Nagy A et al (1990) Embryonic stem cells alone are able to support fetal development in the mouse. Development 110:815–821

    CAS  Google Scholar 

  16. Doetschman T et al (1987) Targetted correction of a mutant HPRT gene in mouse embryonic stem cells. Nature 330:576–578

    Article  CAS  Google Scholar 

  17. Thomas KR, Capecchi MR (1987) Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells. Cell 51:503–512

    Article  CAS  Google Scholar 

  18. National Research Council (1994) Genetically altered mice: a revolutionary research resource. In: Sharing laboratory resources: genetically altered mice: summary of a workshop held at the National Academy of Sciences, 23–24 March 1993. https://www.ncbi.nlm.nih.gov/books/NBK231336/

  19. Bongso A, Fong CY, Ng SC, Ratnam S (1994) Isolation and culture of inner cell mass cells from human blastocysts. Hum Reprod 9:2110–2117

    Article  CAS  Google Scholar 

  20. Thomson JA et al (1998) Embryonic stem cell lines derived from human blastocysts. Science 282:1145–1147

    Article  CAS  Google Scholar 

  21. Tesar PJ et al (2007) New cell lines from mouse epiblast share defining features with human embryonic stem cells. Nature 448:196–199

    Article  CAS  Google Scholar 

  22. Brons IG et al (2007) Derivation of pluripotent epiblast stem cells from mammalian embryos. Nature 448:191–195

    Article  CAS  Google Scholar 

  23. Batlle-Morera L, Smith A, Nichols J (2008) Parameters influencing derivation of embryonic stem cells from murine embryos. Genesis 46:758–767

    Article  Google Scholar 

  24. Tachibana M et al (2013) Human embryonic stem cells derived by somatic cell nuclear transfer. Cell 153:1228–1238

    Article  CAS  Google Scholar 

  25. Oderberg DS (2005) Human embryonic stem cell research: what’s wrong with it? Hum Life Rev 31:21–33

    Google Scholar 

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

    Article  CAS  Google Scholar 

  27. Mascetti VL, Pedersen RA (2016) Contributions of mammalian chimeras to pluripotent stem cell research. Cell Stem Cell 19:163–175

    Article  CAS  Google Scholar 

  28. Muller FJ, Brandl B, Loring JF (2008) Assessment of human pluripotent stem cells with PluriTest. StemBook 2012. Harvard Stem Cell Institute, Cambridge

    Google Scholar 

  29. Waddington CH (1957) The strategy of the genes. Routledge, Abingdon

    Google Scholar 

  30. Gurdon JB (1962) The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. J Embryol Exp Morphol 10:622–640

    CAS  Google Scholar 

  31. Campbell KH, McWhir J, Ritchie WA, Wilmut I (1996) Sheep cloned by nuclear transfer from a cultured cell line. Nature 380:64–66

    Article  CAS  Google Scholar 

  32. Miller RA, Ruddle FH (1976) Pluripotent teratocarcinoma-thymus somatic cell hybrids. Cell 9:45–55

    Article  CAS  Google Scholar 

  33. Ying QL, Nichols J, Evans EP, Smith AG (2002) Changing potency by spontaneous fusion. Nature 416:545–548

    Article  CAS  Google Scholar 

  34. Terada N et al (2002) Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature 416:542–545

    Article  CAS  Google Scholar 

  35. Do JT, Scholer HR (2004) Nuclei of embryonic stem cells reprogram somatic cells. Stem Cells 22:941–949

    Article  CAS  Google Scholar 

  36. Cowan CA, Atienza J, Melton DA, Eggan K (2005) Nuclear reprogramming of somatic cells after fusion with human embryonic stem cells. Science 309:1369–1373

    Article  CAS  Google Scholar 

  37. Schneuwly S, Klemenz R, Gehring WJ (1987) Redesigning the body plan of drosophila by ectopic expression of the homoeotic gene antennapedia. Nature 325:816–818

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  39. Filvaroff EH, Derynck R (1996) Induction of myogenesis in mesenchymal cells by MyoD depends on their degree of differentiation. Dev Biol 178:459–471

    Article  CAS  Google Scholar 

  40. Xie H, Ye M, Feng R, Graf T (2004) Stepwise reprogramming of B cells into macrophages. Cell 117:663–676

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  42. Okita K, Ichisaka T, Yamanaka S (2007) Generation of germline-competent induced pluripotent stem cells. Nature 448:313–317

    Article  CAS  Google Scholar 

  43. Yu J et al (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917–1920

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  45. Park IH et al (2008) Reprogramming of human somatic cells to pluripotency with defined factors. Nature 451:141–146

    Article  CAS  Google Scholar 

  46. Loh YH et al (2010) Reprogramming of T cells from human peripheral blood. Cell Stem Cell 7:15–19

    Article  Google Scholar 

  47. Hacein-Bey-Abina S et al (2003) LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science 302:415–419

    Article  CAS  Google Scholar 

  48. Soldner F et al (2009) Parkinson’s disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell 136:964–977

    Article  CAS  Google Scholar 

  49. Sommer CA et al (2010) Excision of reprogramming transgenes improves the differentiation potential of iPS cells generated with a single excisable vector. Stem Cells 28:64–74

    CAS  Google Scholar 

  50. Ramos-Mejia V et al (2012) Residual expression of the reprogramming factors prevents differentiation of iPSC generated from human fibroblasts and cord blood CD34+ progenitors. PLoS One 7:e35824

    Article  CAS  Google Scholar 

  51. Awe JP et al (2013) Generation and characterization of transgene-free human induced pluripotent stem cells and conversion to putative clinical-grade status. Stem Cell Res Ther 7:87

    Article  CAS  Google Scholar 

  52. Nakagawa M et al (2008) Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol 26:101–106

    Article  CAS  Google Scholar 

  53. Fusaki N, Ban H, Nishiyama A, Saeki K, Hasegawa M (2009) Efficient induction of transgene-free human pluripotent stem cells using a vector based on Sendai virus, an RNA virus that does not integrate into the host genome. Proc Jpn Acad Ser B Phys Biol Sci 85:348–362

    Article  CAS  Google Scholar 

  54. Zhou W et al (2009) Adenoviral gene delivery can reprogram human fibroblasts to induced pluripotent stem cells. Stem Cells 27:2667–2674

    Article  CAS  Google Scholar 

  55. Kim D et al (2009) Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell 4:472–476

    Article  CAS  Google Scholar 

  56. Warren L et al (2010) Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell 7:618–630

    Article  CAS  Google Scholar 

  57. Miyoshi N et al (2011) Reprogramming of mouse and human cells to pluripotency using mature microRNAs. Cell Stem Cell 8:633–638

    Article  CAS  Google Scholar 

  58. Jia F et al (2010) A nonviral minicircle vector for deriving human iPS cells. Nat Methods 7:197–199

    Article  CAS  Google Scholar 

  59. Okita K et al (2011) A more efficient method to generate integration-free human iPS cells. Nat Methods 8:409–412

    Article  CAS  Google Scholar 

  60. Schlaeger TM et al (2015) A comparison of non-integrating reprogramming methods. Nat Biotechnol 33:58–63

    Article  CAS  Google Scholar 

  61. Carapuca E, Azzoni AR, Prazeres DM, Monteiro GA, Mergulhao FJ (2007) Time-course determination of plasmid content in eukaryotic and prokaryotic cells using real-time PCR. Mol Biotechnol 37:120–126

    Article  CAS  Google Scholar 

  62. Gershan JA et al (2005) Immediate transfection of patient-derived leukemia: a novel source for generating cell-based vaccines. Genet Vaccines Ther 3:4

    Article  Google Scholar 

  63. Cohen RN, van der Aa MA, Macaraeg N, Lee AP, Szoka Jr FC (2009) Quantification of plasmid DNA copies in the nucleus after lipoplex and polyplex transfection. J Control Release 135:166–174

    Article  CAS  Google Scholar 

  64. Fliedl L, Kast F, Grillari J, Wieser M, Grillari-Voglauer R (2015) Optimization of a quantitative PCR based method for plasmid copy number determination in human cell lines. New Biotechnol 32:716–719

    Article  CAS  Google Scholar 

  65. Chen ZY, He CY, Ehrhardt A, Kay MA (2003) Minicircle DNA vectors devoid of bacterial DNA result in persistent and high-level transgene expression in vivo. Mol Ther 8:495–500

    Article  CAS  Google Scholar 

  66. Riu E, Chen ZY, Xu H, He CY, Kay MA (2007) Histone modifications are associated with the persistence or silencing of vector-mediated transgene expression in vivo. Mol Ther 15:1348–1355

    Article  CAS  Google Scholar 

  67. Gracey Maniar LE et al (2013) Minicircle DNA vectors achieve sustained expression reflected by active chromatin and transcriptional level. Mol Ther 21:131–138

    Article  CAS  Google Scholar 

  68. Maherali N et al (2008) A high-efficiency system for the generation and study of human induced pluripotent stem cells. Cell Stem Cell 3:340–345

    Article  CAS  Google Scholar 

  69. Hockemeyer D et al (2008) A drug-inducible system for direct reprogramming of human somatic cells to pluripotency. Cell Stem Cell 3:346–353

    Article  CAS  Google Scholar 

  70. Chan EM et al (2009) Live cell imaging distinguishes bona fide human iPS cells from partially reprogrammed cells. Nat Biotechnol 27:1033–1037

    Article  CAS  Google Scholar 

  71. Si-Tayeb K et al (2010) Generation of human induced pluripotent stem cells by simple transient transfection of plasmid DNA encoding reprogramming factors. BMC Dev Biol 10:81

    Article  CAS  Google Scholar 

  72. Van Craenenbroeck K, Vanhoenacker P, Haegeman G (2000) Episomal vectors for gene expression in mammalian cells. Eur J Biochem 267:5665–5678

    Article  Google Scholar 

  73. Nanbo A, Sugden A, Sugden B (2007) The coupling of synthesis and partitioning of EBV's plasmid replicon is revealed in live cells. EMBO J 26:4252–4262

    Article  CAS  Google Scholar 

  74. Leight ER, Sugden B (2001) Establishment of an oriP replicon is dependent upon an infrequent, epigenetic event. Mol Cell Biol 21:4149–4161

    Article  CAS  Google Scholar 

  75. Yates JL, Guan N (1991) Epstein-Barr virus-derived plasmids replicate only once per cell cycle and are not amplified after entry into cells. J Virol 65:483–488

    CAS  Google Scholar 

  76. Kameda T, Smuga-Otto K, Thomson JA (2006) A severe de novo methylation of episomal vectors by human ES cells. Biochem Biophys Res Commun 349:1269–1277

    Article  CAS  Google Scholar 

  77. Yu J et al (2009) Human induced pluripotent stem cells free of vector and transgene sequences. Science 324:797–801

    Article  CAS  Google Scholar 

  78. Krizhanovsky V, Lowe SW (2009) Stem cells: the promises and perils of p53. Nature 460:1085–1086

    Article  CAS  Google Scholar 

  79. Chou BK et al (2011) Efficient human iPS cell derivation by a non-integrating plasmid from blood cells with unique epigenetic and gene expression signatures. Cell Res 21:518–529

    Article  CAS  Google Scholar 

  80. Drozd AM et al (2015) Generation of human iPSCs from cells of fibroblastic and epithelial origin by means of the oriP/EBNA-1 episomal reprogramming system. Stem Cell Res Ther 6:122

    Article  CAS  Google Scholar 

  81. Silva M et al (1996) Erythropoietin can promote erythroid progenitor survival by repressing apoptosis through Bcl-XL and Bcl-2. Blood 88:1576–1582

    CAS  Google Scholar 

  82. Bai H et al (2012) Bcl-xL enhances single-cell survival and expansion of human embryonic stem cells without affecting self-renewal. Stem Cell Res 8:26–37

    Article  CAS  Google Scholar 

  83. Su RJ et al (2013) Efficient generation of integration-free ips cells from human adult peripheral blood using BCL-XL together with Yamanaka factors. PLoS One 8:e64496

    Article  CAS  Google Scholar 

  84. Chou BK et al (2015) A facile method to establish human induced pluripotent stem cells from adult blood cells under feeder-free and xeno-free culture conditions: a clinically compliant approach. Stem Cells Transl Med 4:320–332

    Article  CAS  Google Scholar 

  85. Wen W et al (2016) Enhanced generation of integration-free iPSCs from human adult peripheral blood mononuclear cells with an optimal combination of episomal vectors. Stem Cell Rep 6:873–884

    Article  CAS  Google Scholar 

  86. Okita K et al (2013) An efficient nonviral method to generate integration-free human-induced pluripotent stem cells from cord blood and peripheral blood cells. Stem Cells 31:458–466

    Article  CAS  Google Scholar 

  87. Chen G et al (2011) Chemically defined conditions for human iPSC derivation and culture. Nat Methods 8:424–429

    Article  CAS  Google Scholar 

  88. Frappier L (2012) Contributions of epstein-barr nuclear antigen 1 (EBNA1) to cell immortalization and survival. Virus 4:1537–1547

    Article  CAS  Google Scholar 

  89. Anokye-Danso F et al (2011) Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency. Cell Stem Cell 8:376–388

    Article  CAS  Google Scholar 

  90. Zhang Z et al (2015) MicroRNA-302/367 cluster governs hESC self-renewal by dually regulating cell cycle and apoptosis pathways. Stem Cell Rep 4:645–657

    Article  CAS  Google Scholar 

  91. Subramanyam D et al (2011) Multiple targets of miR-302 and miR-372 promote reprogramming of human fibroblasts to induced pluripotent stem cells. Nat Biotechnol 29:443–448

    Article  CAS  Google Scholar 

  92. Howden SE et al (2015) Simultaneous reprogramming and gene correction of patient fibroblasts. Stem Cell Rep 5:1109–1118

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  94. Goh PA et al (2013) A systematic evaluation of integration free reprogramming methods for deriving clinically relevant patient specific induced pluripotent stem (iPS) cells. PLoS One 8:e81622

    Article  CAS  Google Scholar 

  95. Mack AA, Kroboth S, Rajesh D, Wang WB (2011) Generation of induced pluripotent stem cells from CD34+ cells across blood drawn from multiple donors with non-integrating episomal vectors. PLoS One 6:e27956

    Article  CAS  Google Scholar 

  96. Sadowski I, Ma J, Triezenberg S, Ptashne M (1988) GAL4-VP16 is an unusually potent transcriptional activator. Nature 335:563–564

    Article  CAS  Google Scholar 

  97. Wang Y et al (2011) Reprogramming of mouse and human somatic cells by high-performance engineered factors. EMBO Rep 12:373–378

    Article  CAS  Google Scholar 

  98. Hirai H et al (2011) Radical acceleration of nuclear reprogramming by chromatin remodeling with the transactivation domain of MyoD. Stem Cells 29:1349–1361

    CAS  Google Scholar 

  99. Boyer LA et al (2005) Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 122:947–956

    Article  CAS  Google Scholar 

  100. Schmidt R, Plath K (2012) The roles of the reprogramming factors Oct4, Sox2 and Klf4 in resetting the somatic cell epigenome during induced pluripotent stem cell generation. Genome Biol 13:251

    Article  CAS  Google Scholar 

  101. Zhu G et al (2014) Coordination of engineered factors with TET1/2 promotes early-stage epigenetic modification during somatic cell reprogramming. Stem Cell Rep 2:253–261

    Article  CAS  Google Scholar 

  102. Hirai H, Katoku-Kikyo N, Karian P, Firpo M, Kikyo N (2012) Efficient iPS cell production with the MyoD transactivation domain in serum-free culture. PLoS One 7:e34149

    Article  CAS  Google Scholar 

  103. Federation AJ, Bradner JE, Meissner A (2014) The use of small molecules in somatic-cell reprogramming. Trends Cell Biol 24:179–187

    Article  CAS  Google Scholar 

  104. Li W, Li K, Wei W, Ding S (2013) Chemical approaches to stem cell biology and therapeutics. Cell Stem Cell 13:270–283

    Article  CAS  Google Scholar 

  105. Yan X et al (2016) Generation of induced pluripotent stem cells from human mesenchymal stem cells of parotid gland origin. Am J Transl Res 8:419–432

    Google Scholar 

  106. Baghbaderani BA et al (2016) Detailed characterization of human induced pluripotent stem cells manufactured for therapeutic applications. Stem Cell Rev 12:394–420

    Article  CAS  Google Scholar 

  107. Baghbaderani BA et al (2015) cGMP-manufactured human induced pluripotent stem cells are available for pre-clinical and clinical applications. Stem Cell Rep 5:647–659

    Article  CAS  Google Scholar 

  108. Taapken SM et al (2011) Karotypic abnormalities in human induced pluripotent stem cells and embryonic stem cells. Nat Biotechnol 29:313–314

    Article  CAS  Google Scholar 

  109. Nagai Y (ed) (2013) Sendai virus vector. Springer, Tokyo

    Google Scholar 

  110. Bousse T, Chambers RL, Scroggs RA, Portner A, Takimoto T (2006) Human parainfluenza virus type 1 but not Sendai virus replicates in human respiratory cells despite IFN treatment. Virus Res 121:23–32

    Article  CAS  Google Scholar 

  111. Nishimura K et al (2007) Persistent and stable gene expression by a cytoplasmic RNA replicon based on a noncytopathic variant Sendai virus. J Biol Chem 282:27383–27391

    Article  CAS  Google Scholar 

  112. Fusaki N, Ban H (2013) Induction of human pluripotent stem cells by the Sendai virus vector: establishment of a highly efficient and footprint-free system. In: Nagai Y (ed) Sendai virus vector. Springer, Tokyo, pp 171–183

    Chapter  Google Scholar 

  113. Li HO et al (2000) A cytoplasmic RNA vector derived from nontransmissible Sendai virus with efficient gene transfer and expression. J Virol 74:6564–6569

    Article  CAS  Google Scholar 

  114. Inoue M et al (2003) Nontransmissible virus-like particle formation by F-deficient sendai virus is temperature sensitive and reduced by mutations in M and HN proteins. J Virol 77:3238–3246

    Article  CAS  Google Scholar 

  115. Yoshizaki M et al (2006) Naked Sendai virus vector lacking all of the envelope-related genes: reduced cytopathogenicity and immunogenicity. J Gene Med 8:1151–1159

    Article  CAS  Google Scholar 

  116. Ban H et al (2011) Efficient generation of transgene-free human induced pluripotent stem cells (iPSCs) by temperature-sensitive Sendai virus vectors. Proc Natl Acad Sci U S A 108:14234–14239

    Article  CAS  Google Scholar 

  117. Fujie Y et al (2014) New type of Sendai virus vector provides transgene-free iPS cells derived from chimpanzee blood. PLoS One 9:e113052

    Article  CAS  Google Scholar 

  118. Beers J et al (2015) A cost-effective and efficient reprogramming platform for large-scale production of integration-free human induced pluripotent stem cells in chemically defined culture. Sci Rep 5:11319

    Article  CAS  Google Scholar 

  119. ThermoFischer Scientific (2017) Publications citing the Sendai Virus for iPSC Generation. http://www.thermofisher.com/us/en/home/life-science/stem-cell-research/induced-pluripotent-stem-cells/sendai-virus-reprogramming/cytotune-publications.html?cid=fl-sendaipubs

  120. Nishimura K et al (2011) Development of defective and persistent Sendai virus vector: a unique gene delivery/expression system ideal for cell reprogramming. J Biol Chem 286:4760–4771

    Article  CAS  Google Scholar 

  121. Kato H et al (2006) Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 441:101–105

    Article  CAS  Google Scholar 

  122. Kang X et al (2015) Effects of integrating and non-integrating reprogramming methods on copy number variation and genomic stability of human induced pluripotent stem cells. PLoS One 10:e0131128

    Article  CAS  Google Scholar 

  123. Manzini S, Viiri LE, Marttila S, Aalto-Setala K (2015) A comparative view on easy to deploy non-integrating methods for patient-specific iPSC production. Stem Cell Rev 11:900–908

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  125. Mallon BS et al (2014) Comparison of the molecular profiles of human embryonic and induced pluripotent stem cells of isogenic origin. Stem Cell Res 12:376–386

    Article  CAS  Google Scholar 

  126. Guenther MG et al (2010) Chromatin structure and gene expression programs of human embryonic and induced pluripotent stem cells. Cell Stem Cell 7:249–257

    Article  CAS  Google Scholar 

  127. Johannesson B et al (2014) Comparable frequencies of coding mutations and loss of imprinting in human pluripotent cells derived by nuclear transfer and defined factors. Cell Stem Cell 15:634–642

    Article  CAS  Google Scholar 

  128. Salomonis N et al (2016) Integrated genomic analysis of diverse induced pluripotent stem cells from the progenitor cell biology consortium. Stem Cell Rep 7:110–125

    Article  CAS  Google Scholar 

  129. Ma H et al (2014) Abnormalities in human pluripotent cells due to reprogramming mechanisms. Nature 511:177–183

    Article  CAS  Google Scholar 

  130. Knoepfler P (2014) Stem cell pioneer Masayo Takahashi interview on iPS cells, clinical studies, & more. http://www.ipscell.com/2014/01/stem-cell-pioneer-masayo-takahashi-interview-on-ips-cells-clinical-studies-more/

  131. Wang J et al (2015) Generation of clinical-grade human induced pluripotent stem cells in Xeno-free conditions. Stem Cell Res Ther 6:223

    Article  CAS  Google Scholar 

  132. Wiley LA et al (2016) cGMP production of patient-specific iPSCs and photoreceptor precursor cells to treat retinal degenerative blindness. Sci Rep 6:30742

    Article  CAS  Google Scholar 

  133. Marchetto MC et al (2009) Transcriptional signature and memory retention of human-induced pluripotent stem cells. PLoS One 4:e7076

    Article  CAS  Google Scholar 

  134. Diecke S et al (2015) Novel codon-optimized mini-intronic plasmid for efficient, inexpensive, and xeno-free induction of pluripotency. Sci Rep 5:8081

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Stem Cell Program, Boston Children’s Hospital, Karp RB09213, 1 Blackfan Circle, Boston, MA, 02446, USA

    Thorsten M. Schlaeger

Authors
  1. Thorsten M. Schlaeger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thorsten M. Schlaeger .

Editor information

Editors and Affiliations

  1. Leibniz Research Labs for Biotechnology, Hannover Medical School (MHH), Hannover, Germany

    Ulrich Martin

  2. Leibniz Research Labs for Biotechnology, Hannover Medical School (MHH), Hannover, Germany

    Robert Zweigerdt

  3. Leibniz Research Labs for Biotechnology, Hannover Medical School (MHH), Hannover, Germany

    Ina Gruh

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Schlaeger, T.M. (2017). Nonintegrating Human Somatic Cell Reprogramming Methods. In: Martin, U., Zweigerdt, R., Gruh, I. (eds) Engineering and Application of Pluripotent Stem Cells. Advances in Biochemical Engineering/Biotechnology, vol 163. Springer, Cham. https://doi.org/10.1007/10_2017_29

Download citation

Publish with us

Policies and ethics

Search

Navigation