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Induced pluripotent stem cells and their implication for regenerative medicine

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Abstract

In 2006 Yamanaka’s group showed that stem cells with properties similar to embryonic stem cells could be generated from mouse fibroblasts by introducing four genes. These cells were termed induced pluripotent stem cells (iPSCs). Because iPSCs avoid many of ethical concerns associated with the use of embryonic material, they have great potential in cell-based regenerative medicine. They are suitable also for other various purposes, including disease modelling, personalized cell therapy, drug or toxicity screening and basic research. Moreover, in the future, there might become possible to generate organs for human transplantation. Despite these progresses, several studies have raised the concern for genetic and epigenetic abnormalities of iPSCs that could contribute to immunogenicity of some cells differentiated from iPSCs. Recent methodological improvements are increasing the ease and efficacy of reprogramming, and reducing the genomic modification. However, to minimize or eliminate genetic alternations in the derived iPSC line creation, factor-free human iPSCs are necessary. In this review we discuss recent possibilities of using iPSCs for clinical applications and new advances in field of their reprogramming methods. The main goal of present article was to review the current knowledge about iPSCs and to discuss their potential for regenerative medicine.

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References

  • Adamkov M, Halasova E, Rajcani J, Bencat M, Vybohova D, Rybarova S, Galbavy S (2011) Relation between expression pattern of p53 and survivin in cutaneous basal cell carcinomas. Med Sci Monit 17(3):74–80

    Article  Google Scholar 

  • Aoi T, Yae K, Nakagawa M, Ichisaka T, Okita K, Takahashi K, Chiba T, Yamanaka S (2008) Generation of pluripotent stem cells from adult mouse liver and stomach cells. Science 321:699–702

    Article  CAS  PubMed  Google Scholar 

  • Apostolou E, Hochedlinger K (2011) iPS cells under attack. Nature 474:165–166

    Article  CAS  PubMed  Google Scholar 

  • Bai Q, Desprat R, Klein B, Lemitre JM, De Vos J (2013) Embryonic stem cells or Induced pluripotent stem celles? A DNA integrity perspective. Curr Gene Ther 13(2):93–98

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ben-David U, Benvenisty N (2011) The tumorigenicyty of human embryonic and induced pluripotent stem cells. Nat Rev Cancer 11:268–277

    Article  CAS  PubMed  Google Scholar 

  • Cai S, Chan YS, Kwok-Yan Shum D (2014) Induced pluripotent stem cells and neurological disease models. Acta Physiol Sinica 66(1):55–66

    CAS  PubMed  Google Scholar 

  • Cheng F, Ke Q, Chen F, Bing C, Gao Y, Ye CH, Wang D, Zhang L, Lahn BT, Li W, Xiang AP (2012) Protecting against wayward human induced pluripotent stem cells with a suicide gene. Biomaterials 33:3195–3204

    Article  CAS  PubMed  Google Scholar 

  • Cui CH, Rao L, Cheng L, Xiao L (2009) Generation and application of human iPS cells. Chin Sci Bull 54:9–13

    Article  CAS  Google Scholar 

  • Deng W (2010) Induced pluripotent stem cells: path to new medicines. EMBO Rep 11:161–165

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Diekman BO, Christoforou N, Willard VP, Sun H, Sanchez-Adams J, Leong KW, Guilak F (2012) Cartilage tissue engineering using differentiated and purified induced pluripotent stem cells. PNAS 109:19172–19177

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Dimos JT, Rodolfa KT, Niakan KK, Weisenthal LM, Mitsumoto H, Chung W, Croft GF, Saphier G, Leibel R, Goland R, Wichterle H, Henderson CHE, Eggan K (2008) Induced pluripotent stem cells generated from patients with ALS can be differentiated into moteor neurons. Science 321:1218–1221

    Article  CAS  PubMed  Google Scholar 

  • Drews K, Jozefczuk J, Prigione A, Adjaye J (2012) Human induced pluripotent stem cells: from mechanisms to clinical applications. J Mol Med 90:735–745

    Article  PubMed  Google Scholar 

  • Durnaoglu S, Genc S, Genc K (2011) Patient-specific pluripotent StemCells in neurological diseases. Stem Cells Int 2011:1–17

    Article  Google Scholar 

  • Ebert AD, Yu J, Rose FF, Mattis VB, Lorson CL, Thomson JA, Svendsen CN (2009) Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature 457:277–280

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gallegos TF, Sancho-Martinez I, Belmonte JCI (2013) Advances in cellular reprogramming: moving toward a reprieve from immunogenicity. Immunol Lett 155:14–17

    Article  CAS  PubMed  Google Scholar 

  • González F, Boué S, Belmonte JCI (2011) Methods for making induced pluripotent stem cells: reprogramming á la carte. Nature Rev 12:231–242

    Article  Google Scholar 

  • Halasova E, Adamkov M, Matakova T, Vybohova D, Antosova M, Janickova M, Singliar A, Dobrota D, Jakusova V (2013) Expression of Ki-67, Bcl-2, survivin and p53 proteins in patients with pulmonary carcinoma. Adv Exp Med Biol 756:15–21

    Article  CAS  PubMed  Google Scholar 

  • Hanna J, Wernig M, Markoulaki S, Sun CW, Meissner A, Cassady JP, Beard C, Brambrink T, Wu LC, Townes TM, Jaenisch R (2007) Treatment of sickle cell anemia mouse model with iPS cells generated form autologus skin. Science 318:1920–1923

    Article  CAS  PubMed  Google Scholar 

  • Hanna J, Markoulaki S, Schorderet P, Carey B, Beard B, Wering M, Creyghton M, Steine E, Cassady J, Foreman R, Lenger Ch, Dausman J, Jaenisch R (2008) Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency. Cell 133:250–264

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hargus G, Coopera O, Deleidia M, Levya A, Leea K, Marlowa E, Yowa A, Soldnerb F, Hockemeyerb D, Halletta PJ, Osborna T, Jaenisch R, Isacson O (2010) Differentiated Parkinson patient-derived induced pluripotent stem cells grow in the adult rodent brain and reduce motor asymmetry in Parkinsonian rats. PNAS 107:15921–15926

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Huang CH, Wu JC (2012) Epigenetic modulation of induced pluripotent stem cells: novel therapies and disease models. Drug Discov Today Dis Models 9(4):e153–e160

    Article  PubMed Central  PubMed  Google Scholar 

  • Kim D, Kim CH, Moon J, Chung Y, Chang M, Han B, Ko S, Yang E, Cha K, Lanza R, Kim K (2009) Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell 4:472–476

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ko JY, Kim KI, Park S, Im GI (2014) In vitro chondorgenesis and in vivo repair of osteochondral defect with human induced pluripotent stem cells. Biomaterials 35:3571–3581

    Article  CAS  PubMed  Google Scholar 

  • Lenger CH (2010) IPS cell technology in regenerative medicine. Ann N Y Acad Sci 1192:38–40

    Article  Google Scholar 

  • Li M, Chen M, Han W, Fu X (2010) How far are induced pluripotent stem cells from the clinic? Ageing Res Rev 9:257–264

    Article  CAS  PubMed  Google Scholar 

  • Lu J, Kong X, Luo Ch, Li KK (2013) Application of epigenome-modifying small molecules in induced pluripotent stem cells. Med Res Rev 33(4):790–822

    Article  CAS  PubMed  Google Scholar 

  • Macarthur CC, Fontes A, Ravinder N, Kuninger D, Kaur J, Bailey M, Taliana A, Vemuri MC, Lieu PT (2012) Generation of human-Induced pluripotent stem cells by a nonintegrating RNA sendai virus vector in feeder-free or xeno-free conditions. Stem Cell Int 2012:1–9

    Article  Google Scholar 

  • Masuda S, Wu J, Hishida T, Pandian GN, Sugiyama H, Belmonte JCI (2013) Chemically induced pluripotent stem cells (CiPSCs): a transgene-free approach. J Cell Biol 5:354–355

    CAS  Google Scholar 

  • Medvedev SP, Shevchenko AI, Zakian SM (2010) Induced pluripotent stem cells: problems and advantages when applying them in regenerative medicine. Acta Naturae 2(2):18–28

    PubMed Central  CAS  PubMed  Google Scholar 

  • Miyoshi N, Ishii I, Nagano H, Haraguchi N, Laksmi Dewi D, Kano Y, Nishikawa SH, Tanemura M, Mimori K, Tanaka F, Saito T, Nishimura J, Takemasa I, Mizushima T, Ikeda M, Yamamoto H, Sekimoto M, Doki Y, Mori M (2011) Reprogramming of mouse and human cells to pluripotency using mature MicroRNAs. Cell Stem Cell 8(6):633–638

    Article  CAS  PubMed  Google Scholar 

  • Narsinh K, Narsinh KH, Wu JC (2011) Derivation of induced pluripotent stem cells for cardiovascular disease modeling. Circ Res 108:1146–1156

    Article  CAS  PubMed  Google Scholar 

  • Nelson TJ, Martinez-Fernandez A, Yamada S, Perez-Terzic C, Ikeda Y, Terzic A (2010) Repair of acute myocardial infarction by human stemness factors induced pluripotent stem cells. Circulation 120(5):408–416

    Article  Google Scholar 

  • Nie B, Wang H, Laurent T, Ding S (2012) Cellular reprogramming: a small molecule perspective. Curr Opin Cell Biol 24(6):784–792

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Nsair A, MacLellan WR (2011) Induced pluripotent stem cell for regenerative cardiovascilar therapies and biomedical discovery. Adv Drug Deliv Rev 63:324–330

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Obokata H, Wakayama T, Sasai Y, Kojima K, Vacanti MP, Niwa H, Yamato M, Vacanti CHA (2014) Stimulus- trigger fate conversion of somatic cells into pluripotency. Nature 505:641–647

    Article  CAS  PubMed  Google Scholar 

  • Oh S, Lee CHK, Cho KJ, Lee K, Cho S, Hong S (2012) Technological progress in generation of induced pluripotent stem cells for clinical application. Sci World J 2012:417809

    Article  Google Scholar 

  • Okita K, Yamanaka S (2014) Induced pluripotent stem cells. In: Lanza R, Atala A (eds) Essential of stem cells biology, 3rd edn. Oxford, UK, pp 369–379

    Google Scholar 

  • Okita K, Nakagawa M, Hong HJ, Ichisaka T, Yamanaka S (2008) Generation of mouse induced pluripotent stem cells without viral vectors. Science 322:949–953

    Article  CAS  PubMed  Google Scholar 

  • Papapetrou EP, Lee G, Malani N, Setty M, Riviere I, Tirunagari LM, Kadota K, Roth SL, Giardina P, Viale A, Leslie C, Bushman FD, Studer L, Sadelain M (2011) Genomic safe harbors permit high β-globin transgene expression in thalassemia induced pluripotent stem cells. Nat Biotechnol 29(1):73–78

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • 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(7175):141–146

    Article  CAS  PubMed  Google Scholar 

  • Pouya A, Satarian L, Kiani S, Javan M, Baharvand H (2011) Human induced pluripotent stem cells differentiation into oligodendrocyte progenitors and transplantation in a rat model of optic chiasm demyelination. PLoS ONE 6(11):e27925

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Raya A, Rodriguez-Piza I, Guenechea G, Vassena R, Navarro S, Barrero MJ, Consiglio A, Castellá M, Rio P, Sleep E, Gonzale F, Tiscornia G, Garreta E, Aasen T, Veiga A, Verma IM, Surrallés J, Bueren J, Izpisúa Belmonte JC (2009) Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells. Nature 460:53–59

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Seifinejad A, Tabebordbar M, Baharvand H, Boyer L, Salakdeh GH (2010) Progress and promise towards safe induced pluripotent stem cells for therapy. Stem Cell Rev. 6(2):297–306

    Article  PubMed  Google Scholar 

  • Si-Tayeb K, Noto FK, Nagaoka M, Li J, Battle MA, Duris CH, North PE, Dalton S, Duncan SA (2010) Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells. Hepatology 51:297–305

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Stadtfeld M, Brennand K, Hochedlinger K (2008) Reprogramming of pancreatic beta cells into induced pluripotent stem cells. Curr Biol 18:890–894

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Sugiura M, Kasama Y, Araki R, Hoki Y, Sunayama M, Uda M, Nakamura M, Ando S, Abe M (2014) Induced pluripotent stem cell generation-associated point mutations arise during the initial stages of the conversion of these cells. Stem Cell Reports 2(1):52–63

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Takahashi K, Yamanaka S (2013) Induced pluripotent stem cells in medicine and biology. Development 140(12):2457–2461

    Article  CAS  PubMed  Google Scholar 

  • 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 131:861–972

    Article  CAS  PubMed  Google Scholar 

  • Tanabe K, Takahashi K, Yamanaka S (2014) Induction of pluripotency by defined factors. Proc Jpn Acad Ser B Phys Biol Sci 90(3):83–96

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM (1998) Embryonic stem cell lines derived from human blastocysts. Science 282:1145–1147

    Article  CAS  PubMed  Google Scholar 

  • Tsai SY, Clavel C, Kim S, Ang YS, Grisanti L, Lee DF, Kelley K, Rendl M (2010) Oct4 and Klf4 reprogram dermal papilla cells into induced pluripotent stem cells. Stem Cells 28:221–228

    CAS  PubMed  Google Scholar 

  • Tsuji O, Miura K, Okada Y, Fujiyoshia K, Mukaino M, Nagoshi N, Kitamura K, Kumagai G, Nishino M, Tomisato S, Higashi H, Nagaih T, Katoha H, Kohda K, Matsuzaki Y, Yuzaki M, Ikedai E, Toyamab Y, Nakamura M, Yamanaka S, Okano H (2010) Therapeutic potential of appropriately evaluated safe-induced pluripotent stem cells for spinal cord injury. PNAS 107:12704–12709

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Vitale AM, Wolvetang E, Mackay-Sim A (2011) Induced pluripotent stem cells: a new technology to study human disease. Int J Biochem Cell Biol 43:843–846

    Article  CAS  PubMed  Google Scholar 

  • Wernig M, Zhao JP, 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. PNAS 105(15):5856–5866

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zhang J, Wilson GF, Soerens AG, Koonce CH, Yu J, Palecek SP, Thomson JA, Kamp TJ (2009) Functional cardiomyocytes derived from human induced pluripotent stem cells. Circ Res 104:e30–e41

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zhang Y, Li W, Laurent T, Ding S (2012) Small molecules, big roles: the chemical manipulation of stem cell fate and somatic cell reprogramming. J Cell Sci 125:5609–5620

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Zhou Y, Zeng F (2013) Integration-free methods for generating induced pluripotent stem cells. Genomics Proteomics Bioinform 11:284–287

    Article  CAS  Google Scholar 

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Acknowledgments

This study was supported by the Grant UK No. 55/2014 and by the Grant of Ministry of Health of the Slovak Republic No. 2012/4-UKBA-4.

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Correspondence to Lubos Danisovic.

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Csobonyeiova, M., Polak, S., Koller, J. et al. Induced pluripotent stem cells and their implication for regenerative medicine. Cell Tissue Bank 16, 171–180 (2015). https://doi.org/10.1007/s10561-014-9462-9

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