Biomedical Applications of Induced Pluripotent Stem Cells

Biomedical Applications of Induced Pluripotent Stem Cells

Neveen A. Salem

Biochemistry Department, Faculty of Science, University of Jeddah, Saudi Arabia
Narcotics, Ergogenic Aids and Poisons Department, Medical Research Division, National Research Centre, Egypt

International Journal of stem cell research

Induced pluripotent stem cells (iPSCs) which are efficiently produced from somatic cells by the introduction of four transcription factors (Oct4, Sox2, Klf4, and c-Myc) in fibroblasts could circumvent the restrictions of multipotent stem cells that obligated to differentiate into only several lineage cells and also, the ethical argument about ESCs that causes oocytes and embryo destruction . In addition, iPSCs are powerful tools applicable in biomedicine, cell therapy, pharmacology and toxicology. Therefore, the use of iPSCs in stem cell therapy has immense prospects and offer remarkable applications in regenerative medicine.This review aimed to summarize the most recent findings on iPSCs and focus on their biomedical applications.

Keywords: Biomedical Applications, Induced Pluripotent Stem Cells

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Neveen A. Biomedical Applications of Induced Pluripotent Stem Cells. International Journal of Stem Cell Research. 2019, 2:7 (This article has been withdrawn from International Journal of Stem Cell Research. Please do not use it for any purposes.)


1. Jeevani T (2011): Stem cell Transplantation- Types, Risks and Benefits. J Stem Cell Res Ther 1: 114.
2. Fuchs E, Tumbar T, Guasch G (2004) : Socializing with the neighbors: stem cells and their niche Cell, 116 , pp. 769-778
3. Bongso A, Richards M (2004): History and perspective of stem cell research. In Best Practice & Research Clinical Obstetrics & Gynaecology, eds. N. Fisk & J. Itskovitz, London: Elsevier Ltd.
4. Weissman IL (2004): Stem cells: units of development, units of regeneration, and units in evolution. Cell 100: 157-168.
5. Horie M, Ito A, Kawabe Y, Kamihira M (2011): A Genetically Engineered STO Feeder System Expressing E-Cadherin and Leukemia Inhibitory Factor for Mouse Pluripotent Stem Cell Culture. J Bioprocess Biotechniq S3: 001.
6. Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI et al. (2002): Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13: 4279-4295.
7. Quintana AM, Grosveld GC (2011): Zebrafish as a Model to Characterize TEL2 Function During Development and Cancer. J Carcinogene Mutagene S1: 001.
8. Singh V, Sinha RJ, Sankhwar SN, Mehrotra B, Ahmed N, et al. (2010): Squamous Cell Carcinoma of the Kidney – Rarity Redefi ned: Case Series with Review of Literature. J Cancer Sci Ther 2: 082-085.
9. Majo F, Rochat A, Nicolas M, Jaoudé GA, Barrandon Y (2008): Oligopotent stem cells are distributed throughout the mammalian ocular surface. Nature 456: 250-254.
10. Wyse RD, Dunbar GL, Rossignol J (2014): Use of genetically modified mesenchymal stem cells to treat neurodegenerative diseases. Int J Mol Sci 15: 1719–1745
11. Tuan RS, Boland G, Tuli R (2003): Adult mesenchymal stem cells and cell-based tissue engineering. Arthritis Res Ther 5:32–45
12. Singh, V. K., Kalsan, M., Kumar, N., Saini, A., & Chandra, R. (2015): Induced pluripotent stem cells: applications in regenerative medicine, disease modeling, and drug discovery. Frontiers in cell and developmental biology, 3, 2.‏
13. Bianco P (2014) :Mesenchymal” stem cells. Annu Rev Cell Dev Biol 30: 677–704
14. Alvarez-Gonzalez C, Duggleby R, Vagaska B, Querol S, Gomez SG, Ferretti P, Madrigal A (2013): Cord blood Lin(–)CD45(–) embryonic-like stem cells are a heterogeneous population that lack self-renewal capacity. PloS One 8: e67968
15. Ramakrishna V , Janardhan P, Sudarsanareddy L (2011): Stem Cells and Regenerative Medicine – A Review. Annual Review & Research in Biology 1(4): 79-110.
16. Mountford JC (2008) : Human embryonic stem cells: origins, characteristics and potential for regenerative therapy .Transfus Med, 18 pp. 1-12
17. Ranjeet M (2016): Stem Cell Applications in Regenerative Medicine and Disease Therapeutics. International Journal of Cell Biology: 1–24.
18. Varlakhanova NV, Cotterman, R F, Devries W N , Morgan J , Donahue L R , Murray S, Knowles B B , Knoepfler P S . (2010): Myc maintains embryonic stem cell pluripotency and self-renewal”. Differentiation. 80 (1): 9–19.
19. King N , Perrin J (2014): Ethical issues in stem cell research and therapy”. Stem Cell Research and Therapy. doi:10.1186/scrt474.
20. Osafune K, Caron L, Borowiak M (2008) :Marked differences in differentiation propensity among human embryonic stem cell lines. Nat Biotechnol 26(3): 313-5
21. Takahashi K, Yamanaka S (2006) :Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell; 126(4): 663-76
22. Takahashi K, Tanabe K, Ohnuki M( 2007):Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131: 861–872.
23. Puri, M C, Nagy A (2012): Concise review: Embryonic stem cells versus induced pluripotent stem cells: the game is on. Stem Cells, 30, 10-4.
24. Zhao XY, Li W, Lv Z (2009): iPS cells produce viable mice through tetraploid complementation. Nature; 461: 86–90
25. Dang DT, Pevsner J, Yang VW. (2000): The biology of the mammalian Kruppel-like family of transcription factors. International Journal of Biochemistry & Cell Biology 32(11–12):1103-1121
26. Marchetto M, Yeo G, Kainohana O, Marsala M, Gage F, Muotri A (2009): Transcriptional signature and memory retention of human-induced pluripotent stem cells. PLoS ONE 4(9): e7076
27. Takahashi K, Yamanaka S (2016) : A decade of transcription factor-mediated reprogramming to pluripotency. Nature Reviews Molecular Cell Biology 17(3):183-193
28. Omole, Adekunle Ebenezer, and Adegbenro Omotuyi John Fakoya. (2018): “Ten years of progress and promise of induced pluripotent stem cells: historical origins, characteristics, mechanisms, limitations, and potential applications.” PeerJ :6 e4370.‏
29. Kiskinis E, Eggan K (2010): Progress toward the clinical application of patient-specific pluripotent stem cells. J Clin Invest; 120: 51–59.
30. Saha K, Jaenisch R (2009): Technical challenges in using human induced pluripotent stem cells to model disease. Cell Stem Cell; 5: 584–595
31. Li J, Song W, Song W, Pan G, Zhou J (2014): Advances in understanding the cell types and approaches used for generating induced pluripotent stem cells. J Hematol Oncol 7: 50
32. Ebert AD, Yu J, Rose FF (2009): Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature; 457: 277–280
33. Agarwal S, Loh YH, McLoughlin EM (2010) :Telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients. Nature; 464: 292–296.
34. Li J, Gao G, Yuan T (2009): Cell based vaccination using transplantation of iPSCderived memory B cells. Vaccine; 27(42): 5728-9.
35. Wu SM, Hochedlinger K (2011): Harnessing the potential of induced pluripotent stem cells for regenerative medicine. Nature Cell Biology13(5):497-505
36. Singh V K, Kalsan M, Kumar N, Saini A, Chandra R (2015): Induced pluripotent stem cells: applications in regenerative medicine, disease modeling, and drug discovery. Frontiers in cell and developmental biology, 3:2
37. Stadtfeld, M, Hochedlinger K (2010). Induced pluripotency: history, mechanisms, and applications. Genes & development, 24(20), 2239-2263.‏
38. Kimbrel EA, Lanza R (2015): Current status of pluripotent stem cells: moving the first therapies to the clinic. Nature Reviews Drug Discovery14(10):681-692
39. Ebert A D, Liang P, Wu J C (2012): Induced pluripotent stem cells as a disease modeling and drug screening platform. Journal of cardiovascular pharmacology, 60(4), 408.‏
40. Chun Y S, Chaudhari P, Jang Y Y (2010): Applications of patient-specific induced pluripotent stem cells; focused on disease modeling, drug screening and therapeutic potentials for liver disease. International journal of biological sciences, 6(7), 796.‏
41. O’Connor TP, Crystal RG. Genetic medicines (2006):Treatment strategies for hereditary disorders. Nat Rev Genet;7:261–76
42. Cornu TI, Thibodeau-Beganny S, Guhl E, Alwin S, Eichtinger M, (2008): DNA-binding specificity is a major determinant of the activity and toxicity of zinc-finger nucleases. Mol. Ther. 16:352–58 28.
43. Cowan CA, Atienza J, Melton DA, Eggan K (2005): Nuclear reprogramming of somatic cells after fusion with human embryonic stem cells. Science 309:1369–73 28a.
44. Davis L, Maizels N (2014): Homology-directed repair of DNA nicks via pathways distinct from canonical double-strand break repair. PNAS 111(10):E924–32
45. Ding Q, Lee Y-K, Schaefer EAK, Peters DT, Veres A (2013): A TALEN genome-editing system for generating human stem cell–based disease models. Cell Stem Cell 12:238–51
46. Yusa K, Rashid ST, Strick-Marchand H (2011): Targeted gene correction of α1-antitrypsin defi ciency in induced pluripotent stem cells. Nature;478:391-4.
47. Teoh H K, Cheong S K (2012): Induced pluripotent stem cells in research and therapy. The Malaysian journal of pathology, 34(1), 1-8
48. Amabile G, Meissner A. (2009) :Induced pluripotent stem cells: current progress and poten‐ tial for regenerative medicine. Trends Mol Med;15:59-68
49. Bolton-Maggs PHB, Pasi KJ (2003): Haemophilias A and B. Lancet;361:1801-9.
50. Xu D, Alipio Z, Fink LM, (2009 ): Phenotypic correction of murine hemophilia A using an iPSCs cell-based therapy. Proc Natl Acad Sci USA;106:808-13.
51. Yadav N, Kanjirakkuzhiyil S, Kumar S ( 2009):The therapeutic effect of bone marrow derived liver cells in the phenotypic correction of murine hemophilia A. Blood;114:4552-61
52. Potdar P, Chaudhary S (2017): Current challenges in the therapeutic use of induced pluripotent stem cells (iPSCs) in cancer therapy. Applied Cancer Research, 37(1), 5.‏1-8
53. Choi SM, Liu H, Chaudhari P, Kim Y, Cheng L, Feng J, Sharkis S, Ye Z, Jang YY (2011): Reprogramming of EBV-immortalized B-lymphocyte cell lines into induced pluripotent Stem cells. Blood.;118:1801–5.
54. Lei F, Haque R, Weiler L, Vrana KE, Song J (2009): T lineage differentiation from induced pluripotent stem cells. Cell Immunol.;260:1–5.
55. Milani V, Stangl S, Issels R, Gehrmann M, Wagner B, Hube K, Mayr D, Hiddemann W, Molls M, Multhoff G (2009): Anti-tumor activity of patient-derived NK cells after cell-based immunotherapy – a case report. J Transl Med.;7:50. 3
56. Knorr DA, Ni Z, Hermanson D, Hexum MK, Bendzick L, Cooper LJN, Lee DA, Kaufman DS (2013): Clinical-scale derivation of natural killer cells from human pluripotent stem cells for cancer therapy. Stem Cells Transl Med.;2:274–83.
57. Fujii S , Shimizu K, Okamoto Y, Kunii N, Nakayama T, Motohashi S, Taniguchi M (2013): NKT cells as an ideal anti-tumor immunotherapeutic. Front. Immunol., |
58. Jiang Z, Han Y, Cao X( 2014): Induced pluripotent stem cell (iPSCs) and their application in immunotherapy. Cell Mol Immunol. 11:17–24.
59. Sánchez-Rivera FJ, Jacks T (2015): Applications of the CRISPR-Cas9 system in cancer biology. Nat Rev Cancer. 15:387–95.
60. Menon T, Firth AL, Scripture-Adams DD, Galic Z (2015): Lymphoid regeneration from gene-corrected SCID-X1 subject-derived iPSCs. Cell Stem Cell.;16(4):367–72
61. Ashcroft FM, Rorsman P (2012):Diabetes mellitus and the β cell: the last ten years.Cell. 2012 Mar 16; 148(6):1160-71.
62. Maehr R, Chen S, Snitow M (2009): Generation of pluripotent stem cells from patients with type 1 diabetes. Proc Natl Acad Sci USA;106:15768-73.
63. Ohmine S, Squillace KA, Hartjes KA (2012): Reprogrammed keratinocytes from elderly type 2 diabetes patients suppress senescence genes to acquire induced pluripotency. Aging (Albany NY);4:60-73
64. Wernig M, Zhao JP, Pruszak J(2008): Neurons derived from reprogrammed fi broblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson’s disease. Proc Natl Acad Sci USA;105:5856-61.
65. Lim W F, Inoue-Yokoo T, Tan K S, Lai I M, Sugiyama D. (2013): Hematopoietic cell differentiation from embryonic and induced pluripotent stem cells. Stem Cell Res. Ther. 4:71. doi: 10.1186/scrt222
66. Focosi D, Amabile G (2017): Induced Pluripotent Stem Cell-Derived Red Blood Cells and Platelet Concentrates: From Bench to Bedside. Cells, 7(1), 2-11
67. Kobayashi T, Yamaguchi T, Hamanaka S, Kato-Itoh M, Yamazaki Y, Ibata, M, Hirabayashi, M. (2010): Generation of rat pancreas in mouse by interspecific blastocyst injection of pluripotent stem cells. Cell, 142(5), 787-799.‏
68. Brouwer T P, Paik D T, Barfi I, Han A, Quax P H, Hamming J F, Wu, J C (2018): Autologous iPSC-Based Vaccines Elicit Anti-tumor Responses In Vivo. Cell Stem Cell, 22, 1-13.‏
69. Scudellari M (2016): How iPS cells changed the world. Nature 534(7607):310–312
70. Guha P, Morgan JW, Mostoslavsky G, Rodrigues N P, Boyd A S (2013) :Lack of immune response to differentiated cells derived from syngeneic induced pluripotent stem cells. Cell Stem Cell 12, 407–412
71. Wobus A M, Loser P (2011) :Present state and future perspectives of using pluripotent stem cells in toxicology research. Arch. Toxicol. 85, 79–117
72. Chun Y S, Byun K, Lee B (2011): Induced pluripotent stem cells and personalized medicine: current progress and future perspectives. Anat. Cell Biol. 44, 245–255.
73. Gore A, Li Z, Fung HL, Young JE, Agarwal S, Antosiewicz-Bourget J, Canto I, Gior‐ getti A, Israel MA, Kiskinis E, Lee JH, Loh YH, Manos PD, Montserrat N, Panopoulos AD, Ruiz S, Wilbert ML, Yu J, Kirkness EF, Izpisua Belmonte JC, Rossi DJ, Thomson JA, Eggan K, Daley GQ, Goldstein LS, Zhang K (2011): Somatic Coding Mutations in Human Induced Pluripotent Stem Cells. Nature 471:63-37
74. Hussein SM, Batada NN, Vuoristo S, Ching RW, Autio R, Narva E, Ng S, Sourour M, Hamalainen R, Olsson C, Lundin K, Mikkola M, Trokovic R, Peitz M, Brustle O, Bazett-Jones DP, Alitalo K, Lahesmaa R, Nagy A, Otonkoski T (2011): Copy Number Variation and Selection During Reprogramming to Pluripotency. Nature 471:58-62.