A Review of the Methods for Human iPSC Derivation

  • Nasir Malik
  • Mahendra S. Rao
Part of the Methods in Molecular Biology book series (MIMB, volume 997)

Abstract

The ability to reprogram somatic cells to induced pluripotent stem cells (iPSCs) offers an opportunity to generate pluripotent patient-specific cell lines that can help model human diseases. These iPSC lines could also be powerful tools for drug discovery and the development of cellular transplantation therapies. Many methods exist for generating iPSC lines but those best suited for use in studying human diseases and developing therapies must be of adequate efficiency to produce iPSCs from samples that may be of limited abundance, capable of reprogramming cells from both skin fibroblasts and blood, and footprint-free. Several reprogramming techniques meet these criteria and can be utilized to derive iPSCs in projects with both basic scientific and therapeutic goals. Combining these reprogramming methods with small molecule modulators of signaling pathways can lead to successful generation of iPSCs from even the most recalcitrant patient-derived somatic cells.

Key words

Induced pluripotent stem cells Reprogramming human somatic cells Footprint-free iPSCs Reprogramming with small molecules 

References

  1. 1.
    Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676PubMedCrossRefGoogle Scholar
  2. 2.
    Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872PubMedCrossRefGoogle Scholar
  3. 3.
    Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917–1920PubMedCrossRefGoogle Scholar
  4. 4.
    Park IH, Zhao R, West JA, Yabuuchi A, Huo H, Ince TA, Lerou PH, Lensch MW, Daley GQ (2008) Reprogramming of human somatic cells to pluripotency with defined factors. Nature 451:141–146PubMedCrossRefGoogle Scholar
  5. 5.
    Wernig M, Meissner A, Foreman R, Brambrink T, Ku M, Hochedlinger K, Bernstein BE, Jaenisch R (2007) In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature 448:318–324PubMedCrossRefGoogle Scholar
  6. 6.
    Papapetrou EP, Tomishima MJ, Chambers SM, Mica Y, Reed E, Menon J, Tabar V, Mo Q, Studer L, Sadelain M (2009) Stoichiometric and temporal requirements of Oct4, Sox2, Klf4, and c-Myc expression for efficient human iPSC induction and differentiation. Proc Natl Acad Sci USA 106:12759–12764PubMedCrossRefGoogle Scholar
  7. 7.
    Carey BW, Markoulaki S, Hanna J, Saha K, Gao Q, Mitalipova M, Jaenisch R (2009) Reprogramming of murine and human somatic cells using a single polycistronic vector. Proc Natl Acad Sci USA 106:157–162PubMedCrossRefGoogle Scholar
  8. 8.
    Chang CW, Lai YS, Pawlik KM, Liu K, Sun CW, Li C, Schoeb TR, Townes TM (2009) Polycistronic lentiviral vector for “hit and run” reprogramming of adult skin fibroblasts to induced pluripotent stem cells. Stem Cells 27:1042–1049PubMedCrossRefGoogle Scholar
  9. 9.
    Sommer CA, Stadtfeld M, Murphy GJ, Hochedlinger K, Kotton DN, Mostoslavsky G (2009) Induced pluripotent stem cell generation using a single lentiviral stem cell cassette. Stem Cells 27:543–549PubMedCrossRefGoogle Scholar
  10. 10.
    Soldner F, Hockemeyer D, Beard C, Gao Q, Bell GW, Cook EG, Hargus G, Blak A, Cooper O, Mitalipova M et al (2009) Parkinson’s disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell 136:964–977PubMedCrossRefGoogle Scholar
  11. 11.
    Somers A, Jean JC, Sommer CA, Omari A, Ford CC, Mills JA, Ying L, Sommer AG, Jean JM, Smith BW et al (2010) Generation of transgene-free lung disease-specific human induced pluripotent stem cells using a single excisable lentiviral stem cell cassette. Stem Cells 28:1728–1740PubMedCrossRefGoogle Scholar
  12. 12.
    Stadtfeld M, Nagaya M, Utikal J, Weir G, Hochedlinger K (2008) Induced pluripotent stem cells generated without viral integration. Science 322:945–949PubMedCrossRefGoogle Scholar
  13. 13.
    Zhou W, Freed CR (2009) Adenoviral gene delivery can reprogram human fibroblasts to induced pluripotent stem cells. Stem Cells 27:2667–2674PubMedCrossRefGoogle Scholar
  14. 14.
    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 85:348–362PubMedCrossRefGoogle Scholar
  15. 15.
    Seki T, Yuasa S, Oda M, Egashira T, Yae K, Kusumoto D, Nakata H, Tohyama S, Hashimoto H, Kodaira M et al (2010) Generation of induced pluripotent stem cells from human terminally differentiated circulating T cells. Cell Stem Cell 7:11–14PubMedCrossRefGoogle Scholar
  16. 16.
    Ban H, Nishishita N, Fusaki N, Tabata T, Saeki K, Shikamura M, Takada N, Inoue M, Hasegawa M, Kawamata S, Nishikawa SI (2011) Proc Natl Acad Sci USA 108:14234–14239PubMedCrossRefGoogle Scholar
  17. 17.
    Zhou H, Wu S, Joo JY, Zhu S, Han DW, Lin T, Trauger S, Bien G, Yao S, Zhu Y et al (2009) Generation of induced pluripotent stem cells using recombinant proteins. Cell Stem Cell 4:381–384PubMedCrossRefGoogle Scholar
  18. 18.
    Kim D, Kim CH, Moon JI, Chung YG, Chang MY, Han BS, Ko S, Yang E, Cha KY, Lanza R et al (2009) Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell 4:472–476PubMedCrossRefGoogle Scholar
  19. 19.
    Warren L, Manos PD, Ahfeldt T, Loh YH, Li H, Lau F, Ebina W, Mandal PK, Smith ZD, Meissner A et al (2010) Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell 7:618–630PubMedCrossRefGoogle Scholar
  20. 20.
    Subramanyam D, Lamouille S, Judson RL, Liu JY, Bucay N, Derynck R, Blelloch R (2011) Multiple targets of miR-302 and miR-372 promote reprogramming of human fibroblasts to induced pluripotent stem cells. Nature Biotechnol 29:443–448CrossRefGoogle Scholar
  21. 21.
    Anokye-Danso F, Trivedi CM, Juhr D, Gupta M, Cui Z, Tian Y, Zhang Y, Yang W, Gruber PJ, Epstein JA et al (2011) Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency. Cell Stem Cell 8:376–388PubMedCrossRefGoogle Scholar
  22. 22.
    Miyoshi N, Ishii H, Nagano H, Haraguchi N, Dewi DL, Kano Y, Nishikawa S, Tanemura M, Mimori K, Tanaka F et al (2011) Reprogramming of mouse and human cells to pluripotency using mature microRNAs. Cell Stem Cell 8:633–638PubMedCrossRefGoogle Scholar
  23. 23.
    Kaji K, Norrby K, Paca A, Mileikovsky M, Mohseni P, Woltjen K (2009) Virus-free induction of pluripotency and subsequent excision of reprogramming factors. Nature 458:771–775PubMedCrossRefGoogle Scholar
  24. 24.
    Woltjen K, Michael IP, Mohseni P, Desai R, Mileikovsky M, Hamalainen R, Cowling R, Wang W, Liu P, Gertsenstein M et al (2009) piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature 458:766–770PubMedCrossRefGoogle Scholar
  25. 25.
    Mali P, Chou BK, Yen J, Ye Z, Zou J, Dowey S, Brodsky RA, Ohm JE, Yu W, Baylin SB et al (2010) Butyrate greatly enhances derivation of human induced pluripotent stem cells by promoting epigenetic remodeling and the expression of pluripotency-associated genes. Stem Cells 28:713–720PubMedCrossRefGoogle Scholar
  26. 26.
    Narsinh KH, Jia F, Robbins RC, Kay MA, Longaker MT, Wu JC (2011) Generation of adult human induced pluripotent stem cells using nonviral minicircle DNA vectors. Nature Protoc 6:78–88CrossRefGoogle Scholar
  27. 27.
    Okita K, Nakagawa M, Hyenjong H, Ichisaka T, Yamanaka S (2008) Generation of mouse induced pluripotent stem cells without viral vectors. Science 322:949–953PubMedCrossRefGoogle Scholar
  28. 28.
    Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R et al (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917–1920PubMedCrossRefGoogle Scholar
  29. 29.
    Hu K, Yu J, Suknuntha K, Tian S, Montgomery K, Choi KD, Stewart R, Thomson JA, Slukvin II (2011) Efficient generation of transgene-free induced pluripotent stem cells from normal and neoplastic bone marrow and cord blood mononuclear cells. Blood 117:e109–e119PubMedCrossRefGoogle Scholar
  30. 30.
    Chen G, Gulbranson DR, Hou Z, Bolin JM, Ruotti V, Probasco MD, Smuga-Otto K, Howden SE, Diol NR, Propson NE et al (2011) Chemically defined conditions for human iPSC derivation and culture. Nat Methods 8:24–429Google Scholar
  31. 31.
    Chou BK, Mali P, Huang X, Ye Z, Dowey SN, Resar LM, Zou C, Zhang YA, Tong J, Cheng L (2011) Efficient human iPS cell derivation by a non-integrating plasmid from blood cells with unique epigenetic and gene expression signatures. Cell Res 21:518–529PubMedCrossRefGoogle Scholar
  32. 32.
    Cheng L, Hansen NF, Zhao L, Du Y, Zou C, Donovan FX, Chou BK, Zhou G, Li S, Dowey SN et al (2012) Low incidence of DNA sequence variation in human induced pluripotent stem cells generated by nonintegrating plasmid expression. Cell Stem Cell 10:337–344PubMedCrossRefGoogle Scholar
  33. 33.
    Wakayama T, Perry AC, Zuccotti M, Johnson KR, Yanagimachi R (1998) Full-term development of mice from enucleated oocytes injected with cumulus. Nature 394:369–374PubMedCrossRefGoogle Scholar
  34. 34.
    Noggle S, Fung H-L, Gore A, Martinez H, Satriani KS, Prosser R, Oum K, Paull D, Druckenmiller S, Freeby M et al (2011) Human oocytes reprogram somatic cells to a pluripotent state. Nature 478:70–75PubMedCrossRefGoogle Scholar
  35. 35.
    Huangfu D, Osafune K, Maehr R, Guo W, Eijkelenboom A, Chen S, Melton DA (2008) Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2. Nat Biotechnol 26:1269–1275PubMedCrossRefGoogle Scholar
  36. 36.
    Lin T, Ambasudhan R, Yuan X, Li W, Hilcove S, Abujarour R, Lin X, Hahm HS, Hao E, Hayek A, Ding S (2009) A chemical platform for improved induction of human iPSCs. Nat Methods 6:805–808PubMedCrossRefGoogle Scholar
  37. 37.
    Ichida JK, Blanchard J, Lam K, Son EY, Chung JE, Egli D, Loh KM, Carter AC, DiGiorgio FP, Koszka K et al (2009) A small-molecule inhibitor of TGF-β signaling replaces Sox2 in reprogramming by inducing nanog. Cell Stem Cell 5:491–503PubMedCrossRefGoogle Scholar
  38. 38.
    Esteban MA, Wang T, Qin B, Yang J, Qin D, Cai J, Li W, Weng Z, Chen J, Ni S et al (2010) Vitamin C enhances the generation of mouse and human induced pluripotent stem cells. Cell Stem Cell 6:71–79PubMedCrossRefGoogle Scholar
  39. 39.
    Zhu S, Li W, Zhou H, Wei W, Ambasudhan R, Lin T, Kim J, Zhang K, Ding S (2010) Reprogramming of human primary somatic cells by OCT4 and chemical compounds. Cell Stem Cell 7:651–655PubMedCrossRefGoogle Scholar
  40. 40.
    Yoshida Y, Takahashi K, Okita K, Ichisaka T, Yamanaka S (2009) Hypoxia enhances the generation of induced pluripotent stem cells. Cell Stem Cell 5:237–241PubMedCrossRefGoogle Scholar
  41. 41.
    Boyer LA, Lee TI, Cole MF, Johnstone SE, Levine SS, Zucker JP, Guenther MG, Kumar RM, Murray HL, Jenner RG et al (2005) Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 122:947–956PubMedCrossRefGoogle Scholar
  42. 42.
    Loh YH, Wu Q, Chew LW, Vega VB, Zhang W, Chen X, Bourque G, George J, Leong B, Liu J et al (2006) The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nat Genet 38:431–440PubMedCrossRefGoogle Scholar
  43. 43.
    Kim J, Chu J, Shen X, Wang J, Orkin SH (2008) An extended transcriptional network of pluripotency of embryonic stem cells. Cell 132:1049–1061PubMedCrossRefGoogle Scholar
  44. 44.
    Balasubramanian S, Babai N, Chaudhuri A, Qiu F, Bhattacharya S, Dave BJ, Parameswaran S, Carson SD, Thoreson WB, Sharp JG et al (2009) Non cell-autonomous reprogramming of adult ocular progenitors: generation of pluripotent stem cells without exogenous transcription factors. Stem Cells 27:3053–3062PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Nasir Malik
    • 1
  • Mahendra S. Rao
    • 1
  1. 1.NIH CRM, National Institute of Arthritis and Musculoskeletal and Skin Disorders (NIAMS), National Institutes of Health (NIH)BethesdaUSA

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