Skip to main content

Advertisement

Log in

“Cutting the Mustard” with Induced Pluripotent Stem Cells: An Overview and Applications in Healthcare Paradigm

  • Published:
Stem Cell Reviews and Reports Aims and scope Submit manuscript

Abstract

Treatment of numerous ailments has been made accessible by the advent of genetic engineering, where the self-renewal property has unfolded the mysteries of regeneration, i.e., stem cells. This is narrowed down to pluripotency, the cell property of differentiating into other adult cells. The generation of induced pluripotent stem cells (iPSCs) was a major breakthrough in 2006, which was generated by a cocktail of 4 Yamanaka Factors, following which significant advancements have been reported in medical science and therapeutics. The iPSCs are reprogrammed from somatic cells, and the fascinating results focused on developing authentic techniques for their generation via molecular reprogramming mechanisms, with a plethora of molecules, like NANOG, miRNAs, and DNA modifying agents, etc. The iPSCs have exhibited reliable results in assessing the etiology and molecular mechanisms of diseases, followed by the development of possible treatments and the elimination of risks of immune rejection. The authors formulate a comprehensive review to develop a clear understanding of iPSC generation, their advantages and limitations, with potential challenges associated with their medical utility. In addition, a wide compendium of applications of iPSCs in regenerative medicine and disease modeling has been discussed, alongside bioengineering technologies for iPSC reprogramming, expansion, isolation, and differentiation. The manuscript aims to provide a holistic picture of the booming advancement of iPSC therapy, to attract the attention of global researchers, to investigate this versatile approach in treatment of multiple disorders, subsequently overcoming the challenges, in order to effectively expand its therapeutic window.

Graphical abstract

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Code Availability

Not Applicable.

Data Availability

Not Applicable.

References

  1. Till, J. E., & McCulloch, E. A. (1961). A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiation Research, 14(2), 213–222.

    Article  CAS  PubMed  Google Scholar 

  2. Lan, M. L., Acharya, M. M., Tran, K. K., Bahari-Kashani, J., Patel, N. H., Strnadel, J., Giedzinski, E., & Limoli, C. L. (2012). Characterizing the radioresponse of pluripotent and multipotent human stem cells. PLoS One, 7(12), e50048.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. 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 Development Biology, 3, 2.

    Article  Google Scholar 

  4. Gurdon, J. B. (1962). The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. Journal of Embryology and Experimental Morphology, 10, 622–640.

    CAS  PubMed  Google Scholar 

  5. Wllmut, I., Schnieke, A. E., McWhlr, J., Kind, A. J., & Campbell, K. H. (1997). Viable offspring derived from fetal and adult mammalian cell. Nature, 385, 810–813.

    Article  Google Scholar 

  6. Evans, M. J., & Kaufman, M. H. (1981). Establishment in culture of pluripotential cells from mouse embryos. Nature, 292(5819), 154–156.

    Article  CAS  PubMed  Google Scholar 

  7. Tada, M., Takahama, Y., & Abe, K. (2001). Nakatsul: N, Tada T. Current Biology, 11, 1553–1558.

    Article  CAS  PubMed  Google Scholar 

  8. Thomson, J. A., Itskovitz-Eldor, J., SSS, Michelle, A., Waknitz, J. J., VSM, S., & Jones, J. M. (1998). Embryonic stem cell lines derived from human blastocysts. Science, 282(5391), 1145.

    Article  CAS  PubMed  Google Scholar 

  9. Mary, A., Dayan, J., Leone, G., Postel, C., Fraisse, F., Malle, C., Vallée, T., Klein-Peschanski, C., Viader, F., de la Sayette, V., & Peschanski, D. (2020). Resilience after trauma: The role of memory suppression. Science, 367(6479), eaay8477.

    Article  CAS  PubMed  Google Scholar 

  10. Hanna, J., Markoulaki, S., Schorderet, P., Carey, B. W., Beard, C., Wernig, M., Creyghton, M. P., Steine, E. J., Cassady, J. P., Foreman, R., & Lengner, C. J. (2008). Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency. Cell, 133(2), 250–264.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Marson, A., Foreman, R., Chevalier, B., Bilodeau, S., Kahn, M., Young, R. A., & Jaenisch, R. (2008). Wnt signaling promotes reprogramming of somatic cells to pluripotency. Cell Stem Cell, 3(2), 132.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Mikkelsen, T. S., Hanna, J., Zhang, X., Ku, M., Wernig, M., Schorderet, P., Bernstein, B. E., Jaenisch, R., Lander, E. S., & Meissner, A. (2008). Dissecting direct reprogramming through integrative genomic analysis. Nature, 454(7200), 49–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Park, I. H., Zhao, R., West, J. A., Yabuuchi, A., Huo, H., Ince, T. A., Lerou, P. H., Lensch, M. W., & Daley, G. Q. (2008). Reprogramming of human somatic cells to pluripotency with defined factors. Nature, 451, 141–146.

    Article  CAS  PubMed  Google Scholar 

  14. Kirouac, D. C., & Zandstra, P. W. (2008). The systematic production of cells for cell therapies. Cell Stem Cell, 3(4), 369–381.

    Article  CAS  PubMed  Google Scholar 

  15. Desponts, C. (2008). A combined chemical and genetic approach for the generation of induced pluripotent stem cells. Cell Stem Cell, 2(6), 525–528.

    Article  PubMed  Google Scholar 

  16. Silva, J., Barmndon, O., Nichols, J., Kawagnchi, L., Theunisscn, T. W., & Smith, A. (2008). Promotion of rcprogramming to ground state pluripotcncy by signal inhibition. PLoS Biology, 6(10), e253.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Zhao, Y., Yin, X., Qin, H., Zhu, F., Liu, H., Yang, W., Zhang, Q., Xiang, C., Hou, P., Song, Z., & Liu, Y. (2008). Two supporting factors greatly improve the efficiency of human iPSC generation. Cell Stem Cell, 3(5), 475–479.

    Article  CAS  PubMed  Google Scholar 

  18. Zhou, J., Kang, S., Schadt, C. W., & Garten Jr., C. T. (2008). In vivo reprogramming of adult pancreatic exocrine cells to beta-cells. Nature, 455(7213), 627–632.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Feng, B., Jiang, J., Kraus, P., Ng, J. H., Heng, J. C., Chan, Y. S., Yaw, L. P., Zhang, W., Loh, Y. H., Han, J., & Vega, V. B. (2009). Reprogramming of fibroblasts into induced pluripotent stem cells with orphan nuclear receptor Esrrb. Nature Cell Biology, 11(2), 197–203.

    Article  CAS  PubMed  Google Scholar 

  20. Fong, Y. W., Inouye, C., Yamaguchi, T., Cattoglio, C., Grubisic, I., & Tjian, R. (2011). A DNA repair complex functions as an Oct4/Sox2 coactivator in embryonic stem cells. Cell, 147(1), 120–131.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Li, W., Wei, W., Zhu, S., Zhu, J., Shi, Y., Lin, T., Hao, E., Hayek, A., Deng, H., & Ding, S. (2009). Generation of rat and human induced pluripotent stem cells by combining genetic reprogramming and chemical inhibitors. Cell Stem Cell, 4(1), 16–19.

    Article  PubMed  Google Scholar 

  22. Stadtfeld, M., Maherali, N., Breault, D. T., & Hochedlinger, K. (2008). Defining molecular cornerstones during fibroblast to iPS cell reprogramming in mouse. Cell Stem Cell, 2(3), 230–240.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Stadtfeld, M., Nagaya, M., Utikal, J., Weir, G., & Hochedlinger, K. (2008). Induced pluripotent stem cells generated without viral integration. Science, 322(5903), 945–949.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. 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. Proceedings of the Japan Academy. Series B, Physical and Biological Sciences, 85(8), 348–362.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Gonzalez, F., Monasterio, M. B., Tiscornia, G., Pulido, N. M., Vassena, R., Morera, L. B., Piza, I. R., & Belmonte, J. C. (2009). Generation of mouse-induced pluripotent stem cells by transient expression of a single nonviral polycistronic vector. Proceeding of the Japan Academy Sciences, 106(22), 8918–8922.

    Article  CAS  Google Scholar 

  26. Yusa, K., Rad, R., Takeda, J., & Bradley, A. (2009). Generation of transgene-free induced pluripotent mouse stem cells by the piggyBac transposon. Nature Methods, 6(5), 363–369.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. International Stem Cell Initiative, Adewumi, O., Aflatoonian, B., Ahrlund-Richter, L., Amit, M., Andrews, P. W., et al. (2007). Characterization of human embryonic stem cell lines by the International Stem Cell Initiative. Nature Biotechnology, 25(7), 803–16. https://doi.org/10.1038/nbt1318

    Article  CAS  Google Scholar 

  28. Chiang, C. H., Su, Y., Wen, Z., Yoritomo, N., Ross, C. A., Margolis, R. L., et al. (2011). Integration-free induced pluripotent stem cells derived from schizophrenia patients with a DISC1 mutation. Molecular Psychiatry, 16(4), 358–360. https://doi.org/10.1038/mp.2011.13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Kim, D., Kim, C. H., Moon, J. I., Chung, Y. G., Chang, M. Y., Han, B. S., Ko, S., Yang, E., Cha, K. Y., Lanza, R., & Kim, K. S. (2009). Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell, 4(6), 472.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Yao, L., Chen, R., Wang, P., Zhang, Q., Tang, H., & Sun, H. Generation of induced pluripotent stem cells with high efficiency from human embryonic renal cortical cells. American Journal of Translational Research, 8(11), 4982–4993.

  31. 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. https://doi.org/10.1016/j.cell.2006.07.024

    Article  CAS  PubMed  Google Scholar 

  32. Omole, A. E., & Fakoya, A. O. J. (2018). Ten years of progress and promise of induced pluripotent stem cells: Historical origins, characteristics, mechanisms, limitations, and potential applications. PeerJ, 6, e4370. https://doi.org/10.7717/peerj.4370

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Telpalo-Carpio, S. A., Aguilar-Yañez, J. M., Gonzalez-Garza, M. T., Cruz-Vega, D. E., & Moreno-Cuevas, J. E. (2013). iPS cells generation: An overview of techniques and methods. Journal of Stem Cells & Regenerative Medicine, 9(1), 2–8. Published online 2013 Apr 30. https://doi.org/10.46582/jsrm.0901002

    Article  Google Scholar 

  34. Huang, C., & Wu, J. C. (2012). Epigenetic modulations of induced pluripotent stem cells: Novel therapies and disease models. Drug Discovery Today: Disease Models, 9(4), e153–e160. https://doi.org/10.1016/j.ddmod.2012.02.004

    Article  PubMed  Google Scholar 

  35. Kishigami, S., et al. (2006). Significant improvement of mouse cloning technique by treatment with trichostatin A after somatic nuclear transfer. Biochemical and Biophysical Research Communications, 340, 183–189.

    Article  CAS  PubMed  Google Scholar 

  36. Petrs-Silva, H., Dinculescu, A., Li, Q., Min, S. H., Chiodo, V., Pang, J. J., Zhong, L., Zolotukhin, S., Srivastava, A., Lewin, A. S., & Hauswirth, W. W. (2009). High-efficiency transduction of the mouse retina by tyrosine-mutant AAV serotype vectors. Molecular Therapy, 17(3), 463–471.

    Article  CAS  PubMed  Google Scholar 

  37. Wobus, A. M., & Loser, P. (2011). Present state and future perspectives of using pluripotent stem cells in toxicology research. Archives of Toxicology, 85, 79–117.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Fong, H., Wang, C., Knoferle, J., Walker, D., Balestra, M. E., & Tong, L. M. (2013). Genetic correction of tauopathy phenotypes in neurons derived from human induced pluripotent stem cells. Stem Cell Reports, 1, 226–234.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Howe, S. J., Mansour, M. R., Schwarzwaelder, K., Bartholomae, C., Hubank, M., Kempski, H., et al. (2008). Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients. The Journal of Clinical Investigation, 118(9), 3143–50. https://doi.org/10.1172/JCI35798

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  41. Li, Y., Zhang, Q., Yin, X., Yang, W., Du, Y., Hou, P., et al. (2011). Generation of iPSCs from mouse fibroblasts with a single gene, Oct4, and small molecules. Cell Research, 21(1), 196–204. https://doi.org/10.1038/cr.2010.142

    Article  CAS  PubMed  Google Scholar 

  42. Hochedlinger, K., Yamada, Y., Beard, C., & Jaenisch, R. (2005). Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues. Cell, 121(3), 465–477.

    Article  CAS  PubMed  Google Scholar 

  43. Park, E. T., Gum, J. R., Kakar, S., Kwon, S. W., Deng, G., & Kim, Y. S. (2008). Aberrant expression of SOX2 upregulates MUC5AC gastric foveolar mucin in mucinous cancers of the colorectum and related lesions. International Journal of Cancer, 122(6), 1253–1260. https://doi.org/10.1002/ijc.23225

    Article  CAS  PubMed  Google Scholar 

  44. Ghaleb, A. M., Nandan, M. O., Chanchevalap, S., Dalton, W. B., Hisamuddin, I. M., & Yang, V. W. (2005). Krüppel-like factors 4 and 5: The yin and yang regulators of cellular proliferation. Cell Research, 15(2), 92–96.

    Article  CAS  PubMed  Google Scholar 

  45. Kuttler, F., & Mai, S. (2006). C-Myc, genomic instability and disease. Genome and Disease, 1, 171–190.

    Article  CAS  Google Scholar 

  46. Zhang, G., Shang, B., Yang, P., Cao, Z., Pan, Y., & Zhou, Q. (2012). Induced pluripotent stem cell consensus genes: Implication for the risk of tumorigenesis and cancers in induced pluripotent stem cell therapy. Stem Cells and Development, 21(6), 955–964.

    Article  CAS  PubMed  Google Scholar 

  47. Cheng, K. W., Agarwal, R., Mitra, S., & Mills, G. B. (2013). Rab25 small GTPase mediates secretion of tumor necrosis factor receptor superfamily member 11b (osteoprotegerin) protecting cancer cells from effects of TRAIL. Journal of Genetic Syndromes & Gene Therapy, 4(4), 153.

    Google Scholar 

  48. Ishida, T., Nakao, S., Ueyama, T., et al. (2020). Metabolic remodeling during somatic cell reprogramming to induced pluripotent stem cells: Involvement of hypoxia-inducible factor 1. Inflammation and Regeneration, 40, 8. https://doi.org/10.1186/s41232-020-00117-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Hirschi, K. K., Li, S., & Roy, K. (2014). Induced pluripotent stem cells for regenerative medicine. Annual Review of Biomedical Engineering, 11(16), 277–294.

    Article  Google Scholar 

  50. Judson, R. L., Babiarz, J. E., Venere, M., & Blelloch, R. (2014). Embryonic stem cell–specific microRNAs promote induced pluripotency. Nature Biotechnology, 27(459–61), 17.

    Google Scholar 

  51. Melton, C., Judson, R. L., & Blelloch, R. (2010). Opposing microRNA families regulate self-renewal in mouse embryonic stem cells. Nature, 463, 621–626.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Anokye-Danso, F., Trivedi, C. M., Juhr, D., Gupta, M., Cui, Z., Tian, Y., Zhang, Y., Yang, W., Gruber, P. J., Epstein, J. A., & Morrisey, E. E. (2011). Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency. Cell Stem Cell, 8(4), 376–388.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Huangfu, D., Maehr, R., Guo, W., Eijkelenboom, A., Snitow, M., Chen, A. E., & Melton, D. A. (2008). Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nature Biotechnology, 26(7), 795–797.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Li, Y., Zhang, Q., Yin, X., Yang, W., Du, Y., Hou, P., Ge, J., Liu, C., Zhang, W., Zhang, X., & Wu, Y. (2011). Generation of iPSCs from mouse fibroblasts with a single gene, Oct4, and small molecules. Cell Research, 21(1), 196–204.

    Article  CAS  PubMed  Google Scholar 

  55. Li, W., Tian, E., Chen, Z. X., Sun, G., Ye, P., Yang, S., Lu, D., Xie, J., Ho, T. V., Tsark, W. M., & Wang, C. (2012). Identification of Oct4-activating compounds that enhance reprogramming efficiency. Proceedings of the National Academy of Sciences of the United States of America, 109(20853–58), 22.

    Google Scholar 

  56. Ichida, J. K., Blanchard, J., Lam, K., Son, E. Y., Chung, J. E., Egli, D., Loh, K. M., Carter, A. C., Di Giorgio, F. P., Koszka, K., & Huangfu, D. (2009). A small-molecule inhibitor of Tgf-β signaling replaces Sox2 in reprogramming by inducing Nanog. Cell Stem Cell, 5(5), 491–503.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Lin, T., Ambasudhan, R., Yuan, X., Li, W., Hilcove, S., Abujarour, R., Lin, X., Hahm, H. S., Hao, E., Hayek, A., & Ding, S. (2009). A chemical platform for improved induction of human iPSCs. Nature Methods, 6(11), 805–808.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Buganim, Y., Faddah, D. A., & Jaenisch, R. (2013). Mechanisms and models of somatic cell reprogramming. Nature Reviews. Genetics, 14, 427–439.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Hou, P., Li, Y., Zhang, X., Liu, C., Guan, J., Li, H., Zhao, T., Ye, J., Yang, W., Liu, K., & Ge, J. (2013). Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds. Science, 341(6146), 651–654.

    Article  CAS  PubMed  Google Scholar 

  60. Downing, T. L., Soto, J., Morez, C., Houssin, T., Fritz, A., Yuan, F., Chu, J., Patel, S., Schaffer, D. V., & Li, S. (2013). Biophysical regulation of epigenetic state and cell reprogramming. Nature Materials, 12, 1154–1162.

    Article  CAS  PubMed  Google Scholar 

  61. Fluri, D. A., Tonge, P. D., Song, H., Baptista, R. P., Shakiba, N., Shukla, S., Clarke, G., Nagy, A., & Zandstra, P. W. (2012). Derivation, expansion and differentiation of induced pluripotent stem cells in continuous suspension cultures. Nature Methods, 9, 509–516.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Deng, W., Jacobson, E. C., Collier, A. J., & Plath, K. (2021). The transcription factor code in iPSC reprogramming. Current Opinion in Genetics & Development, 70, 89–96. https://doi.org/10.1016/j.gde.2021.06.003

    Article  CAS  Google Scholar 

  63. Sidhu, K. (2012). Basic principles in generating induced pluripotent stem cells. Progenitor and Stem Cell Technologies and Therapies, 49–63. https://doi.org/10.1533/9780857096074.1.49

  64. Wernig, M., Meissner, A., Foreman, R., Brambrink, T., Ku, M., Hochedlinger, K., Bernstein, B. E., & Jaenisch, R. (2007). In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature., 448, 318–324.

    Article  CAS  PubMed  Google Scholar 

  65. Malik, N., & Rao, M. S. (2013). A review of the methods for human iPSC derivation. Methods in Molecular Biology, 997, 23–33. https://doi.org/10.1007/978-1-62703-348-0_3

    Article  CAS  PubMed  Google Scholar 

  66. Medvedev, S. P., Shevchenko, A. I., & Zakian, S. M. (2010). Induced pluripotent stem cells: Problems and advantages when applying them in regenerative medicine. Acta Naturae, 2(2), 18–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Singh, A., Suri, S., Lee, T., Chilton, J. M., Cooke, M. T., Chen, W., Fu, J., Stice, S. L., Lu, H., McDevitt, T. C., & García, A. J. (2013). Adhesion strength–based, label-free isolation of human pluripotent stem cells. Nature Methods, 10(5), 438–444.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Rais, Y., Zviran, A., Geula, S., Gafni, O., Chomsky, E., Viukov, S., Mansour, A. A., Caspi, I., Krupalnik, V., Zerbib, M., & Maza, I. (2013). Deterministic direct reprogramming of somatic cells to pluripotency. Nature, 502(7469), 65–70.

    Article  CAS  PubMed  Google Scholar 

  69. Kim, J. J., LaGrone, A., Krasny, A., Sullivan, N., et al. (2019). Gentle sorting accelerates generation of genome-edited iPSCs. Nanocellect Biomedical, Inc..

    Google Scholar 

  70. Zhou, Q., Brown, J., Kanarek, A., Rajagopal, J., & Melton, D. A. (2008). In vivo reprogramming of adult pancreatic exocrine cells to β-cells. Nature, 455(7213), 627–632.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Ieda, M., Fu, J. D., Delgado-Olguin, P., Vedantham, V., Hayashi, Y., Bruneau, B. G., & Srivastava, D. (2010). Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors. Cell, 142(3), 375–386.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Qian, L., Huang, Y., Spencer, C. I., Foley, A., Vedantham, V., Liu, L., Conway, S. J., Fu, J. D., & Srivastava, D. (2012). In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes. Nature, 485(7400), 593–598.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Song, K., Nam, Y. J., Luo, X., Qi, X., Tan, W., Huang, G. N., Acharya, A., Smith, C. L., Tallquist, M. D., Neilson, E. G., & Hill, J. A. (2012). Heart repair by reprogramming non-myocytes with cardiac transcription factors. Nature, 485(7400), 599–604.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Vierbuchen, T., Ostermeier, A., Pang, Z. P., Kokubu, Y., Südhof, T. C., & Wernig, M. (2010). Direct conversion of fibroblasts to functional neurons by defined factors. Nature., 463(7284), 1035–1041.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Ambasudhan, R., Talantova, M., Coleman, R., Yuan, X., Zhu, S., Lipton, S. A., & Ding, S. (2011). Direct reprogramming of adult human fibroblasts to functional neurons under defined conditions. Cell Stem Cell, 9(2), 113–118.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Karow, M., Sánchez, R., Schichor, C., Masserdotti, G., Ortega, F., Heinrich, C., Gascón, S., Khan, M. A., Lie, D. C., Dellavalle, A., & Cossu, G. (2012). Reprogramming of pericyte-derived cells of the adult human brain into induced neuronal cells. Cell Stem Cell, 11(4), 471–476.

    Article  CAS  PubMed  Google Scholar 

  77. Huang, P., He, Z., Ji, S., Sun, H., Xiang, D., Liu, C., Hu, Y., Wang, X., & Hui, L. (2011). Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors. Nature., 475(7356), 386–389.

    Article  CAS  PubMed  Google Scholar 

  78. Sekiya, S., & Suzuki, A. (2011). Direct conversion of mouse fibroblasts to hepatocyte-like cells by defined factors. Nature., 475(7356), 390–393.

    Article  CAS  PubMed  Google Scholar 

  79. Efe, J. A., Hilcove, S., Kim, J., Zhou, H., Ouyang, K., Wang, G., Chen, J., & Ding, S. (2011). Conversion of mouse fibroblasts into cardiomyocytes using a direct reprogramming strategy. Nature Cell Biology, 13(3), 215–222.

    Article  CAS  PubMed  Google Scholar 

  80. Thier, M., Wörsdörfer, P., Lakes, Y. B., Gorris, R., Herms, S., Opitz, T., Seiferling, D., Quandel, T., Hoffmann, P., Nöthen, M. M., & Brüstle, O. (2012). Direct conversion of fibroblasts into stably expandable neural stem cells. Cell Stem Cell, 10(4), 473–479.

    Article  CAS  PubMed  Google Scholar 

  81. Margariti, A., Winkler, B., Karamariti, E., Zampetaki, A., Tsai, T. N., Baban, D., Ragoussis, J., Huang, Y., Han, J. D. J., Zeng, L., & Hu, Y. (2012). Direct reprogramming of fibroblasts into endothelial cells capable of angiogenesis and reendothelialization in tissue-engineered vessels. Proceedings of the National Academy of Sciences, 109(34), 13793–13798.

    Article  CAS  Google Scholar 

  82. Karamariti, E., Margariti, A., Winkler, B., Wang, X., Hong, X., Baban, D., Ragoussis, J., Huang, Y., Han, J. D., Wong, M. M., & Sag, C. M. (2013). Smooth muscle cells differentiated from reprogrammed embryonic lung fibroblasts through DKK3 signaling are potent for tissue engineering of vascular grafts. Circulation Research, 112(11), 1433–1443.

    Article  CAS  PubMed  Google Scholar 

  83. Petrs-Silva, H., Dinculescu, A., Li, Q., Min, S. H., Chiodo, V., Pang, J. J., Zhong, L., Zolotukhin, S., Srivastava, A., Lewin, A. S., & Hauswirth, W. W. (2009). High-efficiency transduction of the mouse retina by tyrosine-mutant AAV serotype vectors. Mol., 17(3), 463–471.

    CAS  Google Scholar 

  84. Tan, Q., Lui, P. P., Rui, Y. F., & Wong, Y. M. (2012). Comparison of potentials of stem cells isolated from tendon and bone marrow for musculoskeletal tissue engineering. Tissue Engineering. Part A, 18(7-8), 840–851.

    Article  CAS  PubMed  Google Scholar 

  85. Doherty, A. M., & Fisher, E. (2003). Microcell-mediated chromosome transfer (MMCT): Small cells with huge potential. Mammalian Genome, 14(9), 583–592.

    Article  PubMed  Google Scholar 

  86. Anderson, C. A., Pettersson, F. H., Clarke, G. M., Cardon, L. R., Morris, A. P., & Zondervan, K. T. (2010). Data quality control in genetic case-control association studies. Nature Protocols, 5(9), 1564–1573.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Xiao, X., Wu, Z. C., & Chou, K. C. (2011). A multi-label classifier for predicting the subcellular localization of gram-negative bacterial proteins with both single and multiple sites. PLoS One, 6(6), e20592.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Yoshida, T., Ozawa, Y., Suzuki, K., Yuki, K., Ohyama, M., Akamatsu, W., Matsuzaki, Y., Shimmura, S., Mitani, K., Tsubota, K., & Okano, H. (2014). The use of induced pluripotent stem cells to reveal pathogenic gene mutations and explore treatments for retinitis pigmentosa. Molecular Brain, 7(1), 1–1.

    Article  Google Scholar 

  89. Jiang, Y., Cowley, S. A., Siler, U., Melguizo, D., Tilgner, K., Browne, C., Dewilton, A., Przyborski, S., Saretzki, G., James, W. S., & Seger, R. A. (2012). Derivation and functional analysis of patient-specific induced pluripotent stem cells as an in vitro model of chronic granulomatous disease. Stem Cells, 30(4), 599–611.

    Article  CAS  PubMed  Google Scholar 

  90. Klein, C., Nguyen, D., Liu, C. H., Mizoguchi, A., Bhan, A. K., Miki, H., Takenawa, T., Rosen, F. S., Alt, F. W., Mulligan, R. C., & Snapper, S. B. (2003). Gene therapy for Wiskott-Aldrich syndrome: Rescue of T-cell signaling and amelioration of colitis upon transplantation of retrovirally transduced hematopoietic stem cells in mice. Blood. American Journal of Hematology, 101(6), 2159–2166.

    CAS  Google Scholar 

  91. Suzuki, K., Mitsui, K., Aizawa, E., Hasegawa, K., Kawase, E., Yamagishi, T., Shimizu, Y., Suemori, H., Nakatsuji, N., & Mitani, K. (2008). Highly efficient transient gene expression and gene targeting in primate embryonic stem cells with helper-dependent adenoviral vectors. Proceedings of the National Academy of Sciences, 105(37), 13781–13786.

    Article  CAS  Google Scholar 

  92. Grizot, S., Smith, J., Daboussi, F., Prieto, J., Redondo, P., Merino, N., Villate, M., Thomas, S., Lemaire, L., Montoya, G., & Blanco, F. J. (2009). Efficient targeting of a SCID gene by an engineered single-chain homing endonuclease. Nucleic Acids Research, 37(16), 5405–5419.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Hockemeyer, D., Wang, H., Kiani, S., Lai, C. S., Gao, Q., Cassady, J. P., Cost, G. J., Zhang, L., Santiago, Y., Miller, J. C., & Zeitler, B. (2011). Genetic engineering of human pluripotent cells using TALE nucleases. Nature Biotechnology, 29(8), 731–734.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Khan, I. F., Hirata, R. K., Wang, P. R., Li, Y., Kho, J., Nelson, A., Huo, Y., Zavaljevski, M., Ware, C., & Russell, D. W. (2010). Engineering of human pluripotent stem cells by AAV-mediated gene targeting. Molecular Therapy, 18(6), 1192–1199.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Choi, S. M., Kim, Y., Shim, J. S., Park, J. T., Wang, R. H., Leach, S. D., Liu, J. O., Deng, C., Ye, Z., & Jang, Y. Y. (2013). Efficient drug screening and gene correction for treating liver disease using patient-specific stem cells. Hepatol., 57(6), 2458–2468.

    Article  CAS  Google Scholar 

  96. Osafune, K. (2021). iPSC technology-based regenerative medicine for kidney diseases. Clinical and Experimental Nephrology, 25(6), 574–584. https://doi.org/10.1007/s10157-021-02030-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Nagoshi, N., Okano, H., & Nakamura, M. (2020). Regenerative therapy for spinal cord injury using iPSC technology. Inflammation and Regeneration, 40. https://doi.org/10.1186/s41232-020-00149-0

  98. Peng, S. P., & Copray, S. (2015). Comparison of human primary with human iPS cell-derived dopaminergic neuron grafts in the rat model for Parkinson's disease. Stem Cell Reviews and Reports, 12, 105–120. https://doi.org/10.1007/s12015-015-9623-7

    Article  CAS  Google Scholar 

  99. Ungless, M. A., & Grace, A. A. (2012). Are you or aren’t you? Challenges associated with physiologically identifying dopamine neurons. Trends in Neurosciences, 35(7), 422–430.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Kirkeby, A., Grealish, S., Wolf, D. A., Nelander, J., Wood, J., Lundblad, M., et al. (2012). Generation of regionally specified neural progenitors and functional neurons from human embryonic stem cells under defined conditions. Cell Reports, 1(6), 703–714.

    Article  CAS  PubMed  Google Scholar 

  101. Doi, D., Samata, B., Katsukawa, M., Kikuchi, T., Morizane, A., Ono, Y., et al. (2014). Isolation of human induced pluripotent stem cell-derived dopaminergic progenitors by cell sorting for successful transplantation. Stem Cell Reports, 2(3), 337–350.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Brundin, P., Nilsson, O. G., Strecker, R. E., Lindvall, O., Astedt, B., & Bjorklund, A. (1986). Behavioural effects of human fetal dopamine neurons grafted in a rat model of Parkinson’s disease. Experimental Brain Research, 65(1), 235–240.

    Article  CAS  PubMed  Google Scholar 

  103. Stromberg, I., Almqvist, P., Bygdeman, M., Finger, T. E., Gerhardt, G., Granholm, A. C., et al. (1989). Human fetal mesencephalic tissue grafted to dopamine-denervated striatum of athymic rats: Light- and electron-microscopical histochemistry and in vivo chronoamperometric studies. Journal of Neuroscience, 9(2), 614–624.

    Article  CAS  PubMed  Google Scholar 

  104. Kriks, S., Shim, J. W., Piao, J., Ganat, Y. M., Wakeman, D. R., Xie, Z., et al. (2011). Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson’s disease. Nature, 480(7378), 547–551.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Rhee, Y. H., Ko, J. Y., Chang, M. Y., Yi, S. H., Kim, D., Kim, C. H., et al. (2011). Protein-based human iPS cells efficiently generate functional dopamine neurons and can treat a rat model of Parkinson disease. Journal of Clinical Investigation, 121(6), 2326–2335.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Ohnuki, M., & Takahashi, K. (2015). Present and future challenges of induced pluripotent stem cells. Philosophical Transactions of the Royal Society, 370(1680), 20140367.

    Article  Google Scholar 

  107. Hanna, J., Wernig, M., Markoulaki, S., Sun, C. W., Meissner, A., Cassady, J. P., Beard, C., Brambrink, T., Wu, L. C., Townes, T. M., & Jaenisch, R. (2007). Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science., 318(5858), 1920–1923.

    Article  CAS  PubMed  Google Scholar 

  108. Zhao, T., Zhang, Z. N., Rong, Z., & Xu, Y. (2011). Immunogenicity of induced pluripotent stem cells. Nature., 474(7350), 212–215.

    Article  CAS  PubMed  Google Scholar 

  109. Araki, R., Uda, M., Hoki, Y., Sunayama, M., Nakamura, M., Ando, S., Sugiura, M., Ideno, H., Shimada, A., Nifuji, A., & Abe, M. (2013). Negligible immunogenicity of terminally differentiated cells derived from induced pluripotent or embryonic stem cells. Nature., 494(7435), 100–104.

    Article  CAS  PubMed  Google Scholar 

  110. Guha, P., Morgan, J. W., 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(4), 407–412.

    Article  CAS  PubMed  Google Scholar 

  111. Nakajima, F., Tokunaga, K., & Nakatsuji, N. (2007). Human leukocyte antigen matching estimations in a hypothetical bank of human embryonic stem cell lines in the Japanese population for use in cell transplantation therapy. Stem Cells, 25(4), 983–985.

    Article  CAS  PubMed  Google Scholar 

  112. Nakatsuji, N., Nakajima, F., & Tokunaga, K. (2008). HLA-haplotype banking and iPS cells. Nature Biotechnology, 26(7), 739–740.

    Article  CAS  PubMed  Google Scholar 

  113. Okita, K., Matsumura, Y., Sato, Y., Okada, A., Morizane, A., Okamoto, S., Hong, H., Nakagawa, M., Tanabe, K., Tezuka, K. I., & Shibata, T. (2011). A more efficient method to generate integration-free human iPS cells. Nature Methods, 8(5), 409–412.

    Article  CAS  PubMed  Google Scholar 

  114. 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(5), 861–872.

    Article  CAS  PubMed  Google Scholar 

  115. Yu, J., Vodyanik, M. A., Smuga-Otto, K., Antosiewicz-Bourget, J., Frane, J. L., Tian, S., Nie, J., Jonsdottir, G. A., Ruotti, V., Stewart, R., & Slukvin, I. I. (2007). Induced pluripotent stem cell lines derived from human somatic cells. Science, 318(5858), 1917–1920.

    Article  CAS  PubMed  Google Scholar 

  116. Nishimura, K., Sano, M., Ohtaka, M., Furuta, B., Umemura, Y., Nakajima, Y., Ikehara, Y., Kobayashi, T., Segawa, H., Takayasu, S., & Sato, H. (2011). Development of defective and persistent Sendai virus vector: A unique gene delivery/expression system ideal for cell reprogramming. The Journal of Biological Chemistry, 286(6), 4760–4771.

    Article  CAS  PubMed  Google Scholar 

  117. Warren, L., Manos, P. D., Ahfeldt, T., Loh, Y. H., Li, H., Lau, F., Ebina, W., Mandal, P. K., Smith, Z. D., Meissner, A., Daley, G. Q., Brack, A. S., Collins, J. J., Cowan, C., Schlaeger, T. M., & Rossi, D. J. (2010). Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell, 7(5), 618–630.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Miyazaki, T., Futaki, S., Suemori, H., Taniguchi, Y., Yamada, M., Kawasaki, M., Hayashi, M., Kumagai, H., Nakatsuji, N., Sekiguchi, K., & Kawase, E. (2012). Laminin E8 fragments support efficient adhesion and expansion of dissociated human pluripotent stem cells. Nature Communications, 3(1), 1–11.

    Article  Google Scholar 

  119. Nakagawa, M., Taniguchi, Y., Senda, S., Takizawa, N., Ichisaka, T., Asano, K., et al. (2014). A novel efficient feeder-free culture system for the derivation of human induced pluripotent stem cells. Scientific Reports, 4(1), 1–7. https://doi.org/10.1038/srep03594

  120. Raab, S., Klingenstein, M., Liebau, S., & Linta, L. (2014). A Comparative View on Human Somatic Cell Sources for iPSC Generation. Stem Cells International, 2014, 768391. 12 pages. https://doi.org/10.1155/2014/768391

    Article  PubMed  PubMed Central  Google Scholar 

  121. Giorgetti, A., Montserrat, N., Aasen, T., Gonzalez, F., Rodríguez-Pizà, I., Vassena, R., Raya, A., Boué, S., Barrero, M. J., Corbella, B. A., & Torrabadella, M. (2009). Generation of induced pluripotent stem cells from human cord blood using OCT4 and SOX2. Cell Stem Cell, 5(4), 353.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Haase, A., Olmer, R., Schwanke, K., Wunderlich, S., Merkert, S., Hess, C., Zweigerdt, R., Gruh, I., Meyer, J., Wagner, S., & Maier, L. S. (2009). Generation of induced pluripotent stem cells from human cord blood. Cell Stem Cell, 5(4), 434–441.

    Article  CAS  PubMed  Google Scholar 

  123. Takenaka, C., Nishishita, N., Takada, N., Jakt, L. M., & Kawamata, S. (2010). Effective generation of iPS cells from CD34+ cord blood cells by inhibition of p53. Experimental Hematology, 38, 154–162.

    Article  CAS  PubMed  Google Scholar 

  124. Loh, Y. H., Agarwal, S., Park, I. H., Urbach, A., Huo, H., Heffner, G. C., Kim, K., Miller, J. D., Ng, K., & Daley, G. Q. (2009). Generation of induced pluripotent stem cells from human blood. American Journal of Hematology, 113(22), 5476–5479.

    CAS  Google Scholar 

  125. Staerk, J., Dawlaty, M. M., Gao, Q., Maetzel, D., Hanna, J., Sommer, C. A., Mostoslavsky, G., & Jaenisch, R. (2010). Reprogramming of peripheral blood cells to induced pluripotent stem cells. Cell Stem Cell, 7(1), 20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Seki, T., Yuasa, S., Oda, M., Egashira, T., Yae, K., Kusumoto, D., et al. (2010). Generation of induced pluripotent stem cells from human terminally differentiated circulating T cells. Cell Stem Cell, 7(1), 11–14. https://doi.org/10.1016/j.stem.2010.06.003

    Article  CAS  PubMed  Google Scholar 

  127. Nishishita, N., Ijiri, H., Takenaka, C., Kobayashi, K., Goto, K., Kotani, E., Itoh, T., Mori, H., & Kawamata, S. (2011). The use of leukemia inhibitory factor immobilized on virus-derived polyhedra to support the proliferation of mouse embryonic and induced pluripotent stem cells. Biomaterials, 32(14), 3555–3563.

    Article  CAS  PubMed  Google Scholar 

  128. Wernig, M., Zhao, J. P., Pruszak, J., Hedlund, E., Fu, D., Soldner, F., Broccoli, V., Constantine-Paton, M., Isacson, O., & Jaenisch, R. (2008). Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson's disease. Proceedings of the National Academy of Sciences, 105(15), 5856–5861.

    Article  CAS  Google Scholar 

  129. Zhang, J., Wilson, G. F., Soerens, A. G., Koonce, C. H., Yu, J., Palecek, S. P., Thomson, J. A., & Kamp, T. J. (2009). Functional cardiomyocytes derived from human induced pluripotent stem cells. Circulation, 104(4), e30–e41.

    CAS  Google Scholar 

  130. Nelson, T. J., Martinez-Fernandez, A., Yamada, S., Perez-Terzic, C., Ikeda, Y., & Terzic, A. (2009). Repair of acute myocardial infarction by human stemness factors induced pluripotent stem cells. Circulation, 120(5), 408–416.

    Article  PubMed  PubMed Central  Google Scholar 

  131. Murry, C. E., & Keller, G. (2008). Differentiation of embryonic stem cells to clinically relevant populations: Lessons from embryonic development. Cell, 132(4), 661–680.

    Article  CAS  PubMed  Google Scholar 

  132. Kroon, E., Martinson, L. A., Kadoya, K., Bang, A. G., Kelly, O. G., Eliazer, S., Young, H., Richardson, M., Smart, N. G., Cunningham, J., & Agulnick, A. D. (2008). Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo. Nature Biotechnology, 26(4), 443–452.

    Article  CAS  PubMed  Google Scholar 

  133. Song, Z., Cai, J., Liu, Y., Zhao, D., Yong, J., Duo, S., Song, X., Guo, Y., Zhao, Y., Qin, H., & Yin, X. (2009). Efficient generation of hepatocyte-like cells from human induced pluripotent stem cells. Cell Research, 19(11), 1233–1242.

    Article  PubMed  Google Scholar 

  134. Green, M. D., Chen, A., Nostro, M. C., d'Souza, S. L., Schaniel, C., Lemischka, I. R., Gouon-Evans, V., Keller, G., & Snoeck, H. W. (2011). Generation of anterior foregut endoderm from human embryonic and induced pluripotent stem cells. Nature Biotechnology, 29(3), 267–272.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Spence, J. R., Mayhew, C. N., Rankin, S. A., Kuhar, M. F., Vallance, J. E., Tolle, K., Hoskins, E. E., Kalinichenko, V. V., Wells, S. I., Zorn, A. M., & Shroyer, N. F. (2011). Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature, 470(7332), 105–109.

    Article  PubMed  Google Scholar 

  136. Kobayashi, T., Yamaguchi, T., Hamanaka, S., Kato-Itoh, M., Yamazaki, Y., Ibata, M., Sato, H., Lee, Y. S., Usui, J. I., Knisely, A. S., & Hirabayashi, M. (2010). Generation of rat pancreas in mouse by interspecific blastocyst injection of pluripotent stem cells. Cell, 142(5), 787–799.

    Article  CAS  PubMed  Google Scholar 

  137. Coffin, J. M., & Stoye, J. P. (2009). A new virus for old diseases? Science, 326(5952), 530–531.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Lee, G., Papapetrou, E. P., Kim, H., Chambers, S. M., Tomishima, M. J., Fasano, C. A., Ganat, Y. M., Menon, J., Shimizu, F., Viale, A., & Tabar, V. (2009). Modelling pathogenesis and treatment of familial dysautonomia using patient-specific iPSCs. nature, 461(7262), 402–406.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Moad, M., Pal, D., Hepburn, A. C., Williamson, S. C., Wilson, L., Lako, M., Armstrong, L., Hayward, S. W., Franco, O. E., Cates, J. M., & Fordham, S. E. (2013). A novel model of urinary tract differentiation, tissue regeneration, and disease: Reprogramming human prostate and bladder cells into induced pluripotent stem cells. European Urology, 64(5), 753–761.

    Article  PubMed  PubMed Central  Google Scholar 

  140. Ku, S., Soragni, E., Campau, E., Thomas, E. A., Altun, G., Laurent, L. C., Loring, J. F., Napierala, M., & Gottesfeld, J. M. (2010). Friedreich's ataxia induced pluripotent stem cells model intergenerational GAA· TTC triplet repeat instability. Cell Stem Cell, 7(5), 631–637.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Park, I. H., Arora, N., Huo, H., Maherali, N., Ahfeldt, T., Shimamura, A., Lensch, M. W., Cowan, C., Hochedlinger, K., & Daley, G. Q. (2008). Disease-specific induced pluripotent stem cells. Cell, 134(5), 877–886.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Kaye, J. A., & Finkbeiner, S. (2013). Modeling Huntington's disease with induced pluripotent stem cells. Molecular and Cellular Neurosciences, (56), 50–64.

  143. Tulpule, A., Kelley, J. M., Lensch, M. W., McPherson, J., Park, I. H., Hartung, O., Nakamura, T., Schlaeger, T. M., Shimamura, A., & Daley, G. Q. (2013). Pluripotent stem cell models of Shwachman-diamond syndrome reveal a common mechanism for pancreatic and hematopoietic dysfunction. Cell Stem Cell, 12(6), 727–736.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Stadtfeld, M., Apostolou, E., Akutsu, H., Fukuda, A., Follett, P., Natesan, S., Kono, T., Shioda, T., & Hochedlinger, K. (2010). Aberrant silencing of imprinted genes on chromosome 12qF1 in mouse induced pluripotent stem cells. Nature, 465(7295), 175–181.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Chestkov, I. V., Vasilieva, E. A., Illarioshkin, S. N., Lagarkova, M. A., & Kiselev, S. L. (2014). Patient-specific induced pluripotent stem cells for SOD1-associated amyotrophic lateral sclerosis pathogenesis studies. Acta Naturae, 6(1 (20)), 54–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Briggs, J. A., Mason, E. A., Ovchinnikov, D. A., Wells, C. A., & Wolvetang, E. J. (2013). Concise review: New paradigms for down syndrome research using induced pluripotent stem cells: Tackling complex human genetic disease. Stem Cells Translational Medicine, 2(3), 175–184.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Soejitno, A., & Prayudi, P. K. (2011). The prospect of induced pluripotent stem cells for diabetes mellitus treatment. Therapeutic Advances in Endocrinology and Metabolism, 2(5), 197–210.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Lee, G., & Studer, L. (2011). Modelling familial dysautonomia in human induced pluripotent stem cells. Philosophical Transactions of the Royal Society B: Biological Sciences, 366(1575), 2286–2296.

    Article  CAS  Google Scholar 

  149. Sauer, A. V., Morbach, H., Brigida, I., Ng, Y. S., Aiuti, A., & Meffre, E. (2012). Defective B cell tolerance in adenosine deaminase deficiency is corrected by gene therapy. Journal of Clinical Investigation, 122(6), 2141–2152.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Ebert, A. D., Yu, J., & Rose Jr., F. F. (2009). Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature, 457, 277–280.

    Article  CAS  PubMed  Google Scholar 

  151. Homma, S., Chen, J. C., Rahimov, F., Beermann, M. L., Hanger, K., Bibat, G. M., Wagner, K. R., Kunkel, L. M., Emerson, C. P., & Miller, J. B. (2012). A unique library of myogenic cells from facioscapulohumeral muscular dystrophy subjects and unaffected relatives: Family, disease and cell function. European Journal of Human Genetics, 20(4), 404–410.

    Article  CAS  PubMed  Google Scholar 

  152. Farra, N., Zhang, W. B., Pasceri, P., Eubanks, J. H., Salter, M. W., & Ellis, J. (2012). Rett syndrome induced pluripotent stem cell-derived neurons reveal novel neurophysiological alterations. Molecular Psychiatry, 17(12), 1261–1271.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Xu, D., Alipio, Z., Fink, L. M., Adcock, D. M., Yang, J., Ward, D. C., & Ma, Y. (2009). Phenotypic correction of murine hemophilia A using an iPS cell-based therapy. Proceedings of the National Academy of Sciences, 106(3), 808–813.

    Article  CAS  Google Scholar 

  154. Wang, X. M., Yik, W. Y., Zhang, P., Lu, W., Dranchak, P. K., Shibata, D., Steinberg, S. J., & Hacia, J. G. (2012). The gene expression profiles of induced pluripotent stem cells from individuals with childhood cerebral adrenoleukodystrophy are consistent with proposed mechanisms of pathogenesis. Stem Cell Research & Therapy, 3(5), 1–5.

    Article  Google Scholar 

  155. Filareto, A., Parker, S., Darabi, R., Borges, L., Iacovino, M., Schaaf, T., Mayerhofer, T., Chamberlain, J. S., Ervasti, J. M., McIvor, R. S., & Kyba, M. (2013). An ex vivo gene therapy approach to treat muscular dystrophy using inducible pluripotent stem cells. Nature Communications, 4(1), 1–9.

    Article  Google Scholar 

  156. Rashid, S. T., Corbineau, S., Hannan, N., Marciniak, S. J., Miranda, E., Alexander, G., Huang-Doran, I., Griffin, J., Ahrlund-Richter, L., Skepper, J., & Semple, R. (2010). Modeling inherited metabolic disorders of the liver using human induced pluripotent stem cells. Journal of Clinical Investigation, 120(9), 3127–3136.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Liu, G. H., Barkho, B. Z., Ruiz, S., Diep, D., Qu, J., Yang, S. L., Panopoulos, A. D., Suzuki, K., Kurian, L., Walsh, C., & Thompson, J. (2011). Recapitulation of premature ageing with iPSCs from Hutchinson–Gilford progeria syndrome. Nature, 472(7342), 221–225.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Israel, M. A., Yuan, S. H., Bardy, C., Reyna, S. M., Mu, Y., Herrera, C., Hefferan, M. P., Van Gorp, S., Nazor, K. L., Boscolo, F. S., & Carson, C. T. (2012). Probing sporadic and familial Alzheimer’s disease using induced pluripotent stem cells. Nature, 482(7384), 216–220.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Yazawa, M., Hsueh, B., Jia, X., Pasca, A. M., Bernstein, J. A., Hallmayer, J., & Dolmetsch, R. E. (2011). Using induced pluripotent stem cells to investigate cardiac phenotypes in Timothy syndrome. Nature, 471(7337), 230–234.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Carvajal-Vergara, X., Sevilla, A., D’Souza, S. L., Ang, Y. S., Schaniel, C., Lee, D. F., Yang, L., Kaplan, A. D., Adler, E. D., Rozov, R., & Ge, Y. (2010). Patient-specific induced pluripotent stem-cell-derived models of LEOPARD syndrome. Nature, 465(7299), 808–812.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Savage, R. A., & Artandi, S. E. (2011). Telomere shortening and loss of self-renewal in dyskeratosis congenita iPS cells. Nature, 474(7351), 399–402.

    Article  PubMed  PubMed Central  Google Scholar 

  162. Devine, M. J., Ryten, M., Vodicka, P., Thomson, A. J., Burdon, T., & Houlden, H. (2011). Parkinson’s disease induced pluripotent stem cells with triplication of the αsynuclein locus. Nature Communications, 2, 440.

    Article  PubMed  Google Scholar 

  163. Merkert, S., Schubert, M., Olmer, R., Engels, L., et al. (2019). High-throughput screening for modulators of CFTR activity based on genetically engineered cystic fibrosis disease-specific iPSCs. Stem Cell Reports, 12(6), 1389–1403.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Del Álamo, J. C., Lemons, D., Serrano, R., et al. (1863). High throughput physiological screening of iPSC-derived cardiomyocytes for drug development. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1717–1727.

  165. Mauritz, C., Schwanke, K., Reppel, M., Neef, S., Katsirntaki, K., Maier, L. S., Nguemo, F., Menke, S., Haustein, M., Hescheler, J., & Hasenfuss, G. (2008). Generation of functional murine cardiac myocytes from induced pluripotent stem cells. Circulation, 118(5), 507–517.

    Article  PubMed  Google Scholar 

  166. Zwi, L., Caspi, O., Arbel, G., Huber, I., Gepstein, A., Park, I. H., & Gepstein, L. (2009). Cardiomyocyte differentiation of human induced pluripotent stem cells. Circulation, 120(15), 1513–1523.

    Article  CAS  PubMed  Google Scholar 

  167. Shimoji, K., Yuasa, S., Onizuka, T., Hattori, F., Tanaka, T., Hara, M., Ohno, Y., Chen, H., Egasgira, T., Seki, T., & Yae, K. (2010). G-CSF promotes the proliferation of developing cardiomyocytes in vivo and in derivation from ESCs and iPSCs. Cell Stem Cell, 6(3), 227–237.

    Article  CAS  PubMed  Google Scholar 

  168. Engler, A. J., Carag-Krieger, C., Johnson, C. P., Raab, M., Tang, H. Y., Speicher, D. W., Sanger, J. W., Sanger, J. M., & Discher, D. E. (2008). Embryonic cardiomyocytes beat best on a matrix with heart-like elasticity: Scar-like rigidity inhibits beating. Journal of Cell Science, 121(22), 3794–3802.

    Article  CAS  PubMed  Google Scholar 

  169. Nunes, S. S., Miklas, J. W., Liu, J., Aschar-Sobbi, R., Xiao, Y., Zhang, B., Jiang, J., Massé, S., Gagliardi, M., Hsieh, A., & Thavandiran, N. (2013). Biowire: A platform for maturation of human pluripotent stem cell–derived cardiomyocytes. Nature Methods, 10(8), 781–787.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Yang, L., Soonpaa, M. H., Adler, E. D., Roepke, T. K., Kattman, S. J., Kennedy, M., Henckaerts, E., Bonham, K., Abbott, G. W., Linden, R. M., & Field, L. J. (2008). Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population. Nature, 453(7194), 524–528.

    Article  CAS  PubMed  Google Scholar 

  171. Narazaki, G., Uosaki, H., Teranishi, M., Okita, K., Kim, B., Matsuoka, S., Yamanaka, S., & Yamashita, J. K. (2008). Directed and systematic differentiation of cardiovascular cells from mouse induced pluripotent stem cells. Circulation, 118(5), 498–506.

    Article  PubMed  Google Scholar 

  172. Moretti, A., Bellin, M., Jung, C. B., Thies, T. M., Takashima, Y., Bernshausen, A., Schiemann, M., Fischer, S., Moosmang, S., Smith, A. G., & Lam, J. T. (2010). Mouse and human induced pluripotent stem cells as a source for multipotent Isl1+ cardiovascular progenitors. The FASEB Journal, 24(3), 700–711.

    Article  CAS  PubMed  Google Scholar 

  173. Park, S. W., Jun Koh, Y., Jeon, J., Cho, Y. H., Jang, M. J., Kang, Y., Kim, M. J., Choi, C., Sook Cho, Y., Chung, H. M., & Young, K. G. (2010). Efficient differentiation of human pluripotent stem cells into functional CD34+ progenitor cells by combined modulation of the MEK/ERK and BMP4 signaling pathways. Blood. The American Journal of Hematology, 116(25), 5762–5772.

    CAS  Google Scholar 

  174. Choi, K. D., Yu, J., Smuga-Otto, K., Salvagiotto, G., Rehrauer, W., Vodyanik, M., Thomson, J., & Slukvin, I. (2009). Hematopoietic and endothelial differentiation of human induced pluripotent stem cells. Stem Cells, 27(3), 559–567.

    Article  CAS  PubMed  Google Scholar 

  175. Sirenko, O., Crittenden, C., Anson, B., Hesley, J., Chen, Y. W., Callamaras, N., & Cromwell, E. F. (2011). Live cell beating assay using human iPSC-derived cardiomyocytes for evaluation of drug efficacy and toxicity. Detail, 3000, 4000.

  176. Mali, P., Ye, Z., Hommond, H. H., Yu, X., Lin, J., Chen, G., Zou, J., & Cheng, L. (2008). Improved efficiency and pace of generating induced pluripotent stem cells from human adult and fetal fibroblasts. Stem Cells, 26(8), 1998–2005.

    Article  CAS  PubMed  Google Scholar 

  177. Shi, Y., Do, J. T., Desponts, C., Hahm, H. S., Schöler, H. R., & Ding, S. (2008). A combined chemical and genetic approach for the generation of induced pluripotent stem cells. Cell Stem Cell, 2(6), 525–528.

    Article  CAS  PubMed  Google Scholar 

  178. Hu, B. Y., & Zhang, S. C. (2009). Differentiation of spinal motor neurons from pluripotent human stem cells. Nature Protocols, 4(9), 1295–1304.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Hu, B. Y., Du, Z. W., & Zhang, S. C. (2009). Differentiation of human oligodendrocytes from pluripotent stem cells. Nature Protocols, 4(11), 1614–1622.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Lee, G., Chambers, S. M., Tomishima, M. J., & Studer, L. (2010). Derivation of neural crest cells from human pluripotent stem cells. Nature Protocols, 5(4), 688–701.

    Article  CAS  PubMed  Google Scholar 

  181. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Zhou, J., Su, P., Li, D., Tsang, S., Duan, E., & Wang, F. (2010). High-efficiency induction of neural conversion in human ESCs and human induced pluripotent stem cells with a single chemical inhibitor of transforming growth factor beta superfamily receptors. Stem Cells, 28(10), 1741–1750.

    Article  CAS  PubMed  Google Scholar 

  183. Haque, A., Adnan, N., Motazedian, A., Akter, F., Hossain, S., Kutsuzawa, K., Nag, K., Kobatake, E., & Akaike, T. (2015). An engineered N-cadherin substrate for differentiation, survival, and selection of pluripotent stem cell-derived neural progenitors. PLoS One, 10(8), e0135170.

    Article  PubMed  PubMed Central  Google Scholar 

  184. Kuo, Y. C., & Huang, M. J. (2012). Material-driven differentiation of induced pluripotent stem cells in neuron growth factor-grafted poly (ε-caprolactone)-poly (β-hydroxybutyrate) scaffolds. Biomaterials, 33(23), 5672–5682.

    Article  CAS  PubMed  Google Scholar 

  185. Keung, A. J., Asuri, P., Kumar, S., & Schaffer, D. V. (2012). Soft microenvironments promote the early neurogenic differentiation but not self-renewal of human pluripotent stem cells. Integrative Biology, 4(9), 1049–1058. https://doi.org/10.1039/c2ib20083j

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Saha, K., Keung, A. J., Irwin, E. F., Li, Y., Little, L., Schaffer, D. V., & Healy, K. E. (2008). Substrate modulus directs neural stem cell behavior. Biophysical Journal, 95(9), 4426–4438.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Ankam, S., Suryana, M., Chan, L. Y., Moe, A. A., Teo, B. K., Law, J. B., Sheetz, M. P., Low, H. Y., & Yim, E. K. (2013). Substrate topography and size determine the fate of human embryonic stem cells to neuronal or glial lineage. Acta Biomaterialia, 9(1), 4535–4545.

    Article  CAS  PubMed  Google Scholar 

  188. Soldner, F., Hockemeyer, D., Beard, C., Gao, Q., Bell, G. W., Cook, E. G., Hargus, G., Blak, A., Cooper, O., Mitalipova, M., & Isacson, O. (2009). Parkinson's disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell, 136(5), 964–977.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Dimos, J. T., Rodolfa, K. T., Niakan, K. K., Weisenthal, L. M., Mitsumoto, H., Chung, W., Croft, G. F., Saphier, G., Leibel, R., Goland, R., & Wichterle, H. (2008). Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Journal of Science, 321(5893), 1218–1221.

    CAS  Google Scholar 

  190. Karumbayaram, S., Novitch, B. G., Patterson, M., Umbach, J. A., Richter, L., Lindgren, A., Conway, A. E., Clark, A. T., Goldman, S. A., Plath, K., & Wiedau-pazos, M. (2009). Directed differentiation of human-induced pluripotent stem cells generates active motor neurons. Stem Cells, 27(4), 806–811.

    Article  CAS  PubMed  Google Scholar 

  191. Marchetto, M. C., Carromeu, C., Acab, A., Yu, D., Yeo, G. W., Mu, Y., Chen, G., Gage, F. H., & Muotri, A. R. (2010). A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells. Cell, 143(4), 527–539.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. Brennand, K. J., Simone, A., Jou, J., Gelboin-Burkhart, C., Tran, N., Sangar, S., Li, Y., Mu, Y., Chen, G., Yu, D., & McCarthy, S. (2011). Modelling schizophrenia using human induced pluripotent stem cells. Nature, 473(7346), 221–225.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  193. Wang, A., Tang, Z., Park, I. H., Zhu, Y., Patel, S., Daley, G. Q., & Li, S. (2011). Induced pluripotent stem cells for neural tissue engineering. Biomaterials, 32(22), 5023–5032.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  194. Tsuji, O., Miura, K., Okada, Y., Fujiyoshi, K., Mukaino, M., Nagoshi, N., Kitamura, K., Kumagai, G., Nishino, M., Tomisato, S., & Higashi, H. (2010). Therapeutic potential of appropriately evaluated safe-induced pluripotent stem cells for spinal cord injury. Proceedings of the National Academy of Sciences, 107(28), 12704–12709.

    Article  CAS  Google Scholar 

  195. Si-Tayeb K, Noto FK, Sepac A, Sedlic F, Bosnjak ZJ, Lough JW, Duncan SA. Generation of human induced pluripotent stem cells by simple transient transfection of plasmid DNA encoding reprogramming factors. BMC Developmental Biology 2010; 10(1): 1-0.

  196. Sullivan, G. J., Hay, D. C., Park, I. H., Fletcher, J., Hannoun, Z., Payne, C. M., Dalgetty, D., Black, J. R., Ross, J. A., Samuel, K., & Wang, G. (2010). Generation of functional human hepatic endoderm from human induced pluripotent stem cells. Journal of Hepatology, 51(1), 329–335.

    Article  CAS  Google Scholar 

  197. Chen, Y. F., Tseng, C. Y., Wang, H. W., Kuo, H. C., Yang, V. W., & Lee, O. K. (2012). Rapid generation of mature hepatocyte-like cells from human induced pluripotent stem cells by an efficient three-step protocol. Journal of Hepatology, 55(4), 1193–1203.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

E.M. would like to acknowledge the support from the National Institute of Biomedical Imaging and Bioengineering (5T32EB009035).

Author information

Authors and Affiliations

Authors

Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, or took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Corresponding authors

Correspondence to Tapan Behl or Ebrahim Mostafavi.

Ethics declarations

Conflicts of Interest/Competing Interests

The authors declare no conflict of interest.

Ethics Approval

Not Applicable.

Consent to Participate

Not Applicable.

Consent for Publication

All the authors listed have approved the manuscript for publication in Stem Cell Reviews and Reports.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Behl, T., Kaur, I., Sehgal, A. et al. “Cutting the Mustard” with Induced Pluripotent Stem Cells: An Overview and Applications in Healthcare Paradigm. Stem Cell Rev and Rep 18, 2757–2780 (2022). https://doi.org/10.1007/s12015-022-10390-4

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12015-022-10390-4

Keywords

Navigation