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Clinical Applications of Induced Pluripotent Stem Cells – Stato Attuale

  • Chavali Kavyasudha
  • Dannie Macrin
  • K. N. ArulJothi
  • Joel P. Joseph
  • M. K. Harishankar
  • Arikketh DeviEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1079)

Abstract

In an adult human body, somatic stem cells are present in small amounts in almost all organs with the function of general maintenance and prevention of premature aging. But, these stem cells are not pluripotent and are unable to regenerate large cellular loss caused by infarctions or fractures especially in cells with limited replicative ability such as neurons and cardiomyocytes. These limitations gave rise to the idea of inducing pluripotency to adult somatic cells and thereby restoring their regeneration, replication and plasticity. Though many trials and research were focused on inducing pluripotency, a solid breakthrough was achieved by Yamanaka in 2006. Yamanaka’s research identified 4 genes (OCT-4, SOX-2, KLF-4 and c-MYC) as the key requisite for inducing pluripotency in any somatic cells (iPSCs). Our study, reviews the major methods used for inducing pluripotency, differentiation into specific cell types and their application in both cell regeneration and disease modelling. We have also highlighted the current status of iPSCs in clinical applications by analysing the registered clinical trials. We believe that this review will assist the researchers to decide the parameters such as induction method and focus their efforts towards clinical application of iPSCs.

Keywords

Disease modelling Non-integrative gene transfer OSKM Factors Regenerative therapy 

Abbreviations

OCT-4

Octamer Transcription factor 4

SOX-2

SRY (Sex Determining Region-Y)-related high mobility group box protein 2

KLF-4

Kruppel-like factor -4

MYC

Myelocytomatosis oncogene

iPSCs

induced Pluripotent Stem Cells

OSKM factors

OCT4, SOX2, KLF4, MYC factors

PSCs

Pluripotent Stem Cells

ESCs

Embryonic Stem Cells

ICM

Inner Cell Mass

hES cells

human Embryonic Stem cells

bHLHZ

basic Helix-Loop-Helixzipper

LIF

Leukemia Inhibitory Factor

TAD

Transactivation Domain

WNT

Wingless-type MMTV (Mouse Mammary Tumor Virus)

TGF-β 1

Transforming Growth Factor beta 1

NF-kB

Nuclear Factor kappa-light-chain-enhancer of activated B cells

mTOR

mechanistic Target of Rapamycin

NOTCH 1

Notch homologue 1

NGF

Nerve Growth Factor

ERK1 and ERK2

Extracellular Signal-Regulated Kinase 1/2

LET- 7

lethal-7

MuLV

Murine Leukemia virus

Tet

Tetracycline

DOX

Doxycycline

cDNA

complementary DNA

PB transposon

Piggybac transposon

MI

Myocardial infarction

EB

Embryoid Bodies

CSD

Cold Shock Domain

CCHC Zinc Fingers

Cys2HisCys Zinc Fingers

HIV

Human Immunodeficiency Virus

BMP2 and BMP4

Bone Morphogenetic Proteins 2 & 4

FGF

Fibroblast Growth Factor

FlK1

Foetal Liver Kinase 1

MCPs

Multipotent Cardiovascular Progenitors

CM

Cardiomyocytes

EC

Endothelial cells

SMC

Smooth Muscle Cells

IGF-1

Insulin like Growth Factor – 1

PIPAAm

Poly (N-isopropylacrylamide)

HNA

Human Nuclear Antigen

cTnT

Cardiac Troponin T

AD

Alzheimer’s disease

PD

Parkinson’s disease

GMEM

Glasgow’s Minimum Essential Medium

KO-SR

KnockOut – Serum Replacer

NEAA

Non-essential amino acids

PDGF

Platelet-derived Growth Factor

PDAPP

PDGF promoter Driven Amyloid Precursor Protein

MGE

Medial ganglionic eminence

SOD1

Superoxide dismutase 1

ALS

Amyotrophic lateral sclerosis

MSCs

Mesenchymal Stem Cells

OPG/RANKL

Osteoprotegerin/Receptor Activator of Nuclear Factor kappa-B Ligand

GF – iPSCs

Gingival Fibroblast – iPSCs

sAD

sporadic Alzheimer’s Disease

APPDP

Amyloid-β Precursor Protein gene Duplication

ER

Endoplasmic Reticulum

HCM

Hypertrophic Cardiomyopathy

DCM

Dilated Cardiomyopathy

BTHS

Barth Syndrome

iPSC-CMs

induced pluripotent derived cardiomyocytes

DM1

Muscular Dystrophy

COPD

Chronic Obstructive Pulmonary Disease

AMD

Age-related Macular Degeneration

CAD

Coronary Artery Disease

ATCC

American Type Culture Collection

Notes

Conflict of Interest

The authors declare no conflict of interest.

References

  1. Aasen T, Raya A, Barrero MJ, Garreta E, Consiglio A, Gonzalez F et al (2008) Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes. Nat Biotechnol 26(11):1276–1284.  https://doi.org/10.1038/nbt.1503 CrossRefPubMedGoogle Scholar
  2. Adhikary S, Eilers M (2005) Transcriptional regulation and transformation by Myc proteins. Nat Rev Mol Cell Biol 6(8):635–645.  https://doi.org/10.1038/nrm1703 CrossRefPubMedGoogle Scholar
  3. Arnold I, Watt FM (2001) c-Myc activation in transgenic mouse epidermis results in mobilization of stem cells and differentiation of their progeny. Curr Biol 11(8):558–568.  https://doi.org/10.1016/S0960-9822(01)00154-3 CrossRefPubMedGoogle Scholar
  4. Avilion AA, Nicolis SK, Pevny LH, Perez L, Vivian N, Lovell-Badge R (2003) Multipotent cell lineages in early mouse development on SOX2 function. Genes Dev 17:126–140.  https://doi.org/10.1101/gad.224503 CrossRefPubMedPubMedCentralGoogle Scholar
  5. Balzer E, Moss EG (2007) Localization of the developmental timing regulator Lin28 to mRNP complexes, P-bodies and stress granules. RNA Biol 4(1):16–25.  https://doi.org/10.4161/rna.4.1.4364 CrossRefPubMedGoogle Scholar
  6. Ben-porath I, Thomson MW, Carey VJ, Ge R, George W, Regev A, Weinberg R a (2008) An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat Genet 40(5):499–507.  https://doi.org/10.1038/ng.127.An CrossRefPubMedPubMedCentralGoogle Scholar
  7. Boyer LA, Tong IL, Cole MF, Johnstone SE, Levine SS, Zucker JP et al (2005) Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 122(6):947–956.  https://doi.org/10.1016/j.cell.2005.08.020 CrossRefPubMedPubMedCentralGoogle Scholar
  8. Büssing I, Slack FJ, Großhans H (2008) let-7 microRNAs in development, stem cells and cancer. Trends Mol Med 14(9):400–409.  https://doi.org/10.1016/j.molmed.2008.07.001 CrossRefPubMedGoogle Scholar
  9. Cartwright P (2005) LIF/STAT3 controls ES cell self-renewal and pluripotency by a Myc-dependent mechanism. Development 132(5):885–896.  https://doi.org/10.1242/dev.01670 CrossRefPubMedGoogle Scholar
  10. Chang D, Lee N, Park I, Choi C, Jeon I, Kwon J et al (2013) Therapeutic potential of human induced pluripotent stem cells in experimental stroke. Cell Transplant 22(8):1427–1440.  https://doi.org/10.3727/096368912X657314 CrossRefPubMedGoogle Scholar
  11. Chen J, Bao JC, Cai CX (2003) Fabrication, characterization and electrocatalysis of an ordered carbon nanotube electrode. Chin J Chem 21(6):665–669.  https://doi.org/10.1016/S0022-2836(02)01449-3 CrossRefGoogle Scholar
  12. Chen LW, Kuang F, Wei LC, Ding YX, Yung KKL, Chan YS (2011) Potential application of induced pluripotent stem cells in cell replacement therapy for Parkinson’ s disease. CNS & Neurol Disord 10:449–458CrossRefGoogle Scholar
  13. Cole MD, Nikiforov MA (2006) Transcriptional activation by the Myc oncoprotein. Curr Top Microbiol Immunol 302:33–50.  https://doi.org/10.1007/3-540-32952-8_2 CrossRefPubMedGoogle Scholar
  14. Cowan CA (2005) Nuclear reprogramming of somatic cells after fusion with human embryonic stem cells. Science 309(5739):1369–1373.  https://doi.org/10.1126/science.1116447 CrossRefPubMedGoogle Scholar
  15. Csobonyeiova M, Polak S, Zamborsky R, Danisovic L (2017) iPS cell technologies and their prospect for bone regeneration and disease modeling: a mini review. J Adv Res 8(4):321–327.  https://doi.org/10.1016/j.jare.2017.02.004 CrossRefPubMedPubMedCentralGoogle Scholar
  16. Dang DT, Pevsner J, Yang VW (2000) The biology of the mammalian Krüppel-like family of transcription factors. Int J Biochem Cell Biol 32(11–12):1103–1121.  https://doi.org/10.1016/S1357-2725(00)00059-5 CrossRefPubMedPubMedCentralGoogle Scholar
  17. Darr H, Benvenisty N (2009) Genetic analysis of the role of the reprogramming gene LIN-28 in human embryonic stem cells. Stem Cells (Dayton, Ohio) 27(2):352–362.  https://doi.org/10.1634/stemcells.2008-0720 CrossRefGoogle Scholar
  18. Dimos JT, Rodolfa KT, Niakan KK, Weisenthal LM, Mitsumoto H, Chung W et al (2008) Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science 321(5893):1218–1221.  https://doi.org/10.1126/science.1158799 CrossRefPubMedGoogle Scholar
  19. Dubois NC, Adolphe C, Ehninger A, Wang RA, Robertson EJ, Trumpp A (2008) Placental rescue reveals a sole requirement for c-Myc in embryonic erythroblast survival and hematopoietic stem cell function. Development 135(14):2455–2465.  https://doi.org/10.1242/dev.022707 CrossRefPubMedGoogle Scholar
  20. Ebert AD, Yu J, Rose FFR Jr, Mattis VB, Christian L, Thomson JA, Svendsen CN (2009) Induced pluripotent stem cells from a spinal muscular atrophy patient. NIH Public Access 457(7227):277–280.  https://doi.org/10.1038/nature07677.Induced CrossRefGoogle Scholar
  21. Fong H, Hohenstein KA, Donovan PJ (2008) Regulation of self-renewal and Pluripotency by Sox2 in human embryonic stem cells. Stem Cells 26(8):1931–1938.  https://doi.org/10.1634/stemcells.2007-1002 CrossRefPubMedGoogle Scholar
  22. Fujiwara N, Shimizu J, Takai K, Arimitsu N, Saito A, Kono T et al (2013) Restoration of spatial memory dysfunction of human APP transgenic mice by transplantation of neuronal precursors derived from human iPS cells. Neurosci Lett 557(PB):129–134.  https://doi.org/10.1016/j.neulet.2013.10.043 CrossRefPubMedGoogle Scholar
  23. Geiman DE, Ton-That H, Johnson JM, Yang VW (2000) Transactivation and growth suppression by the gut-enriched Krüppel-like factor (Krüppel-like factor 4) are dependent on acidic amino acid residues and protein-protein interaction. Nucleic Acids Res 28(5):1106–1113.  https://doi.org/10.1093/nar/28.5.1106 CrossRefPubMedPubMedCentralGoogle Scholar
  24. González F, Boué S, Belmonte JCI (2016) Methods for making induced pluripotent stem cells: reprogramming à la carte. Nat Rev Genet 17(2):122.  https://doi.org/10.1038/nrg2937 CrossRefGoogle Scholar
  25. Guilak F, Cohen D, Estes B, Gimble J, Liedtke W, Chen C (2009) Control of stem cell fate by physical interactions with the extracellular matrix. Cell Stem Cell 5(1):17–26.  https://doi.org/10.1016/j.stem.2009.06.016.Control CrossRefPubMedPubMedCentralGoogle Scholar
  26. Haase A, Olmer R, Schwanke K, Wunderlich S, Merkert S, Hess C et al (2009) Generation of induced pluripotent stem cells from human cord blood. Cell Stem Cell 5(4):434–441.  https://doi.org/10.1016/j.stem.2009.08.021 CrossRefPubMedGoogle Scholar
  27. Hanna J, Saha K, Pando B, van Zon J, Lengner CJ, Creyghton MP et al (2009) Direct cell reprogramming is a stochastic process amenable to acceleration. Nature 462(7273):595–601.  https://doi.org/10.1038/nature08592 CrossRefPubMedPubMedCentralGoogle Scholar
  28. Hargus G, Cooper O, Deleidi M, Levy A, Lee K, Marlow E et al (2010) Differentiated Parkinson patient-derived induced pluripotent stem cells grow in the adult rodent brain and reduce motor asymmetry in Parkinsonian rats. Proc Natl Acad Sci 107(36):15921–15926.  https://doi.org/10.1073/pnas.1010209107 CrossRefPubMedGoogle Scholar
  29. Hay DC, Sutherland L, Clark J, Burdon T (2004) Oct-4 knockdown induces similar patterns of endoderm and trophoblast differentiation markers in human and mouse embryonic stem cells. Stem Cells 22(2):225–235.  https://doi.org/10.1634/stemcells.22-2-225 CrossRefPubMedGoogle Scholar
  30. Heo I, Joo C, Cho J, Ha M, Han J, Kim VN (2008) Lin28 mediates the terminal Uridylation of let-7 precursor MicroRNA. Mol Cell 32(2):276–284.  https://doi.org/10.1016/j.molcel.2008.09.014 CrossRefPubMedGoogle Scholar
  31. Israel MA, Yuan SH, Bardy C, Reyna SM, Mu Y, Herrera C et al (2012) Probing sporadic and familial Alzheimer’s disease using induced pluripotent stem cells. Nature 482(7384):216–220.  https://doi.org/10.1038/nature10821 CrossRefPubMedPubMedCentralGoogle Scholar
  32. Jeon OH, Panicker LM, Lu Q, Chae JJ, Feldman RA, Elisseeff JH (2016) Human iPSC-derived osteoblasts and osteoclasts together promote bone regeneration in 3D biomaterials. Sci Rep 6(May):26761.  https://doi.org/10.1038/srep26761 CrossRefPubMedPubMedCentralGoogle Scholar
  33. Jia F, Wilson KD, Sun N, Gupta DM, Huang M, Robbins RC et al (2010) A nonviral Minicircle vector for deriving human iPS cells. Nat Methods 7(3):197–199.  https://doi.org/10.1038/nmeth.1426.A CrossRefPubMedPubMedCentralGoogle Scholar
  34. Kallas A, Pook M, Trei A, Maimets T (2014) SOX2 is regulated differently from NANOG and OCT4 in human embryonic stem cells during early differentiation initiated with sodium butyrate. Stem Cells Int 2014(2):1–12.  https://doi.org/10.1155/2014/298163 CrossRefGoogle Scholar
  35. Karakikes I, Vittavat Termglinchan JCW (2014) Human induced pluripotent stem cell models of inherited cardiomyopathies Ioannis. Curr Opin Cardiol 29(3):214–219.  https://doi.org/10.1002/ana.22528.Toll-like CrossRefPubMedPubMedCentralGoogle Scholar
  36. Kehat I, Kenyagin-Karsenti D (2001) Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes. J Clin Investig 108(3):407–414.  https://doi.org/10.1172/JCI200112131.Introduction CrossRefPubMedGoogle Scholar
  37. Kim JB, Sebastiano V, Wu G, Araúzo-Bravo MJ, Sasse P, Gentile L et al (2009) Oct4-induced Pluripotency in adult neural stem cells. Cell 136(3):411–419.  https://doi.org/10.1016/j.cell.2009.01.023 CrossRefPubMedGoogle Scholar
  38. Kim MO, Kim S-H, Cho Y-Y, Nadas J, Jeong C-H, Yao K et al (2012) ERK1 and ERK2 regulate embryonic stem cell self-renewal through phosphorylation of Klf4. Nat Struct Mol Biol 19(3):283–290.  https://doi.org/10.1038/nsmb.2217 CrossRefPubMedGoogle Scholar
  39. Kleine-Kohlbrecher D, Adhikary S, Eilers M (2006) Mechanisms of transcriptional repression by Myc. Curr Top Microbiol Immunol 302:51–62.  https://doi.org/10.1007/3-540-32952-8_3 CrossRefPubMedGoogle Scholar
  40. Knoepfler PS, Cheng PF, Eisenman RN (2002) N-myc is essential during neurogenesis for the rapid expansion of progenitor cell populations and the inhibition of neuronal differentiation. Genes Dev 16(20):2699–2712.  https://doi.org/10.1101/gad.1021202 CrossRefPubMedPubMedCentralGoogle Scholar
  41. Kondo T, Asai M, Tsukita K, Kutoku Y, Ohsawa Y, Sunada Y et al (2013) Modeling Alzheimer’s disease with iPSCs reveals stress phenotypes associated with intracellular Aβ and differential drug responsiveness. Cell Stem Cell 12(4):487–496.  https://doi.org/10.1016/j.stem.2013.01.009 CrossRefPubMedGoogle Scholar
  42. Kopp JL, Ormsbee BD, Desler M, Rizzino A (2008) Small increases in the level of Sox2 trigger the differentiation of mouse embryonic stem cells. Stem Cells 26(4):903–911.  https://doi.org/10.1634/stemcells.2007-0951 CrossRefPubMedGoogle Scholar
  43. Ku S, Soragni E, Campau E, Thomas EA, Altun G, Laurent LC et al (2010) Friedreich’s ataxia induced pluripotent stem cells model intergenerational GAA TTC triplet repeat instability. Cell Stem Cell 7(5):631–637.  https://doi.org/10.1016/j.stem.2010.09.014.Friedreich CrossRefPubMedPubMedCentralGoogle Scholar
  44. Laflamme MA, Chen KY, Naumova AV, Muskheli V, Fugate JA, Dupras SK et al (2007) Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts. Nat Biotechnol 25(9):1015–1024.  https://doi.org/10.1038/nbt1327 CrossRefPubMedGoogle Scholar
  45. Li Z, Zhao J, Li Q, Yang W, Song Q, Li W, Liu J (2010) KLF4 promotes hydrogen-peroxide-induced apoptosis of chronic myeloid leukemia cells involving the bcl-2/bax pathway. Cell Stress Chaperones 15(6):905–912.  https://doi.org/10.1007/s12192-010-0199-5 CrossRefPubMedPubMedCentralGoogle Scholar
  46. Lian Q, Zhang Y, Zhang J, Zhang HK, Wu X, Zhang Y et al (2010) Functional mesenchymal stem cells derived from human induced pluripotent stem cells attenuate limb ischemia in mice. Circulation 121(9):1113–1123.  https://doi.org/10.1161/CIRCULATIONAHA.109.898312 CrossRefPubMedGoogle Scholar
  47. Liu H, Ye Z, Kim Y, Sharkis S, Jang Y-Y (2010) Generation of endoderm-derived human induced pluripotent stem cells from primary hepatocytes. Hepatology (Baltimore, Md) 51(5):1810–1819.  https://doi.org/10.1002/hep.23626 CrossRefGoogle Scholar
  48. Lo Sardo V, Ferguson W, Erikson GA, Topol EJ, Baldwin KK, Torkamani A (2016) Influence of donor age on induced pluripotent stem cells. Nat Biotechnol 35(1):69–74.  https://doi.org/10.1038/nbt.3749 CrossRefPubMedGoogle Scholar
  49. Loh YH, Wu Q, Chew JL, Vega VB, Zhang W, Chen X et al (2006) The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nat Genet 38(4):431–440.  https://doi.org/10.1038/ng1760 CrossRefPubMedGoogle Scholar
  50. Loh Y, Agarwal S, Park I, Urbach A, Huo H, Heffner GC et al (2009) Generation of induced pluripotent stem cells from human blood. Hematopoiesis Stem Cells 113(22):1–3.  https://doi.org/10.1182/blood-2009-02-204800.The CrossRefGoogle Scholar
  51. Maherali N, Hochedlinger K (2008) Guidelines and techniques for the generation of induced pluripotent stem cells. Cell Stem Cell Elsevier Inc 3:595.  https://doi.org/10.1016/j.stem.2008.11.008 CrossRefGoogle Scholar
  52. Maherali N, Sridharan R, Xie W, Utikal J, Eminli S, Arnold K et al (2007) Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution. Cell Stem Cell 1(1):55–70.  https://doi.org/10.1016/j.stem.2007.05.014 CrossRefPubMedGoogle Scholar
  53. Masui S, Nakatake Y, Toyooka Y, Shimosato D, Yagi R, Takahashi K et al (2007) Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells. Nat Cell Biol 9(6):625–635.  https://doi.org/10.1038/ncb1589 CrossRefPubMedGoogle Scholar
  54. Masumoto H, Ikuno T, Takeda M, Fukushima H, Marui A, Katayama S et al (2014) Human iPS cell-engineered cardiac tissue sheets with cardiomyocytes and vascular cells for cardiac regeneration. Sci Rep 4(1):6716.  https://doi.org/10.1038/srep06716 CrossRefPubMedPubMedCentralGoogle Scholar
  55. Matthias S, Nagaya M, Utikal J, Weir G, K. H. (2008) Induced pluripotent stem cells generated without viral integration. Science 322(5903):945–949.  https://doi.org/10.1126/science.1162494.Induced CrossRefGoogle Scholar
  56. Mauritz C, Martens A, Rojas SV, Schnick T, Rathert C, Schecker N et al (2011) Induced pluripotent stem cell (iPSC)-derived Flk-1 progenitor cells engraft, differentiate, and improve heart function in a mouse model of acute myocardial infarction. Eur Heart J 32(21):2634–2641.  https://doi.org/10.1093/eurheartj/ehr166 CrossRefPubMedGoogle Scholar
  57. McMahon JA, Takada S, Zimmerman LB, Fan CM, Harland RM, McMahon AP (1998) Noggin-mediated antagonism of BMP signaling is required for growth and patterning of the neural tube and somite. Genes Dev 12(10):1438–1452.  https://doi.org/10.1101/gad.12.10.1438 CrossRefPubMedPubMedCentralGoogle Scholar
  58. Medvedev SP, Shevchenko AI, Zakian SM (2010) Induced pluripotent stem cells: problems and advantages when applying them in regenerative medicine. Acta Nat 2(2):18–28. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/22649638%5Cnhttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3347549Google Scholar
  59. Moss E, Lee R, Ambros V (1997) Control of developmental timing by the cold shock domain protein Lin-28 and its regulation by the lin-4 RNA. Cell 88(5):637–646CrossRefPubMedGoogle Scholar
  60. Mummery C, Ward D, Van Den Brink CE, Bird SD, Doevendans PA, Opthof T et al (2002) Cardiomyocyte differentiation of mouse and human embryonic stem cells. J Anat 200(3):233–242.  https://doi.org/10.1046/j.1469-7580.2002.00031.x CrossRefPubMedPubMedCentralGoogle Scholar
  61. Muratore CR, Rice HC, Srikanth P, Callahan DG, Shin T, Benjamin LNP et al (2014) The familial alzheimer’s disease APPV717I mutation alters APP processing and Tau expression in iPSC-derived neurons. Hum Mol Genet 23(13):3523–3536.  https://doi.org/10.1093/hmg/ddu064 CrossRefPubMedPubMedCentralGoogle Scholar
  62. Nakagawa M, Koyanagi M, Tanabe K, Takahashi K, Ichisaka T, Aoi T et al (2007) Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol 26(1):101–106CrossRefPubMedGoogle Scholar
  63. Nelson TJ, Martinez-Fernandez A, Yamada S, Perez-Terzic C, Ikeda Y, Terzic A (2009) Repair of acute myocardial infarction with iPS induced by human stemness factors. Circulation 120(5):408.  https://doi.org/10.1161/CIRCULATIONAHA.109.865154.Repair CrossRefPubMedPubMedCentralGoogle Scholar
  64. Nicholas CR, Chen J, Tang Y, Southwell DG, Chalmers N, Vogt D et al (2013) Functional maturation of hPSC-derived forebrain interneurons requires an extended timeline and mimics human neural development. Cell Stem Cell 12(5):573–586.  https://doi.org/10.1016/j.stem.2013.04.005 CrossRefPubMedPubMedCentralGoogle Scholar
  65. Nichols J, Zevnik B, Anastassiadis K, Niwa H, Klewe-Nebenius D, Chambers I et al (1998) Formation of pluripotent stem cells in the mammalian embryo dependes on the POU transcription factor Oct4. Cell 95(3):379–391.  https://doi.org/10.1016/S0092-8674(00)81769-9 CrossRefPubMedGoogle Scholar
  66. Niwa H (2001) Molecular mechanism to maintain stem cell renewal of ES cells. Cell Struct Funct 26(3):137–148.  https://doi.org/10.1247/csf.26.137 CrossRefPubMedGoogle Scholar
  67. Niwa H, Miyazaki J, Smith AG (2000) Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nat Genet 24(4):372–376.  https://doi.org/10.1038/74199 CrossRefPubMedGoogle Scholar
  68. Okawa H, Kayashima H, Sasaki JI, Miura J, Kamano Y, Kosaka Y et al (2016) Scaffold-free fabrication of Osteoinductive cellular constructs using mouse gingiva-derived induced pluripotent stem cells. Stem Cells Int 2016(9):1–11.  https://doi.org/10.1155/2016/6240794 CrossRefGoogle Scholar
  69. Okita MN, Hyenjong H, Tomoko Ichisaka SY (2008) Generation of mouse induced pluripotent stem cells without viral vectors. Science 322(1998):949–953CrossRefPubMedGoogle Scholar
  70. Okubo T (2005) Nmyc plays an essential role during lung development as a dosage-sensitive regulator of progenitor cell proliferation and differentiation. Development 132(6):1363–1374.  https://doi.org/10.1242/dev.01678 CrossRefPubMedGoogle Scholar
  71. Ota K, Matsui M, Milford EL, Mackin GA, Weiner HL, Hafler DA (1990) T-cell recognition of an immuno-dominant myelin basic protein epitope in multiple sclerosis. Nature 346(6280):183–187.  https://doi.org/10.1038/346183a0 CrossRefPubMedGoogle Scholar
  72. Pandya H, Shen MJ, Ichikawa DM, Sedlock AB, Choi Y, Johnson KR et al (2017) Differentiation of human and murine induced pluripotent stem cells to microglia-like cells. Nat Neurosci 20(5):753–759.  https://doi.org/10.1038/nn.4534 CrossRefPubMedPubMedCentralGoogle Scholar
  73. Park I-H, Arora N, Huo H, Maherali N, Ahfeldt T, Shimamura A et al (2008) Disease-specific induced pluripotent stem cells. Cell 134(5):877–886.  https://doi.org/10.1016/j.cell.2008.07.041 CrossRefPubMedPubMedCentralGoogle Scholar
  74. Pawani H, Bhartiya D (2013) Pluripotent stem cells for cardiac regeneration: overview of recent advances & emerging trends. Indian J Med Res 137(2):270–282. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/23563370%5Cnhttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3657850PubMedPubMedCentralGoogle Scholar
  75. Pesce M, Schöler HR (2000) Oct-4: control of totipotency and germline determination. Mol Reprod Dev 55(4):452–457.  https://doi.org/10.1002/(SICI)1098-2795(200004)55:4<452::AID-MRD14>3.0.CO;2-S CrossRefPubMedGoogle Scholar
  76. Qiu C, Ma Y, Wang J, Peng S, Huang Y (2009) Lin28-mediated post-transcriptional regulation of Oct4 expression in human embryonic stem cells. Nucleic Acids Res 38(4):1240–1248.  https://doi.org/10.1093/nar/gkp1071 CrossRefPubMedPubMedCentralGoogle Scholar
  77. Richards M, Tan S, Tan J, Chan W, Bongso A (2004) The transcriptome profile of human embryonic stem cells as defined by SAGE. Stem Cells 22(1):51–64.  https://doi.org/10.1634/stemcells.22-1-51 CrossRefPubMedGoogle Scholar
  78. Rizzino A (2009) Sox2 and Oct-3/4: a versatile pair of master regulators that orchestrate the self-renewal and pluripotency of embryonic stem cells. Wiley Interdiscip Rev Syst Biol Med 1(2):228–236.  https://doi.org/10.1002/wsbm.12 CrossRefPubMedPubMedCentralGoogle Scholar
  79. Saha K, Jaenisch R (2010) Technical challenges in using human induced pluripotent stem cells to model disease. Cell Stem Cell 5(6):584–595.  https://doi.org/10.1016/j.stem.2009.11.009.Technical CrossRefGoogle Scholar
  80. Scholer HR, Ruppert S, Suzuki N, Chowdhury K, Gruss P (1990) New type of POU domain in germ line-specific protein Oct-4. Nature 344(6265):435–439.  https://doi.org/10.1038/344435a0 CrossRefPubMedGoogle Scholar
  81. Segev H, Kenyagin Karsenti D, Fishman B, Gerecht Nir S, Ziskind A, Amit M et al (2005) Molecular analysis of cardiomyocytes derived from human embryonic stem cells. Develop Growth Differ 47(5):295–306.  https://doi.org/10.1111/j.1440-169X.2005.00803.x CrossRefGoogle Scholar
  82. Sheyn D, Ben-David S, Shapiro G, Demel S, Bez M, Ornelas L et al (2016) Human induced pluripotent stem cells differentiate into functional mesenchymal stem cells and repair bone defects. Stem Cells Transl Med 5:1447–1460.  https://doi.org/10.1002/stem.1607 CrossRefPubMedPubMedCentralGoogle Scholar
  83. Shie JL, Chen ZY, Fu M, Pestell RG, Tseng CC (2000) Gut-enriched Krüppel-like factor represses cyclin D1 promoter activity through Sp1 motif. Nucleic Acids Res 28(15):2969–2976. Retrieved from http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=102679&tool=pmcentrez&rendertype=abstract CrossRefPubMedPubMedCentralGoogle Scholar
  84. Sugii S, Kida Y, Kawamura T, Suzuki J, Vassena R, Yin Y-Q et al (2010) Human and mouse adipose-derived cells support feeder-independent induction of pluripotent stem cells. Proc Natl Acad Sci 107(8):3558–3563.  https://doi.org/10.1073/pnas.0910172106 CrossRefPubMedGoogle Scholar
  85. Sun N, Yazawa M, Liu J, Han L, Sanchez-Freire V, Abilez OJ, Navarrete EG, Hu S, Wang L, Lee A, Pavlovic A, Lin S, Chen R, Hajjar RJ (2012) Patient-specific induced pluripotent stem cells as model for familial dilated Cardiomyopthy. Sci Transl Med 4(130):130ra47.  https://doi.org/10.1126/scitranslmed.3003552.Patient-Specific CrossRefPubMedPubMedCentralGoogle Scholar
  86. Swistowski A, Peng J, Liu Q, Mali P, Rao MS, Cheng L, Zeng X (2010) Efficient generation of functional dopaminergic neurons from human induced pluripotent stem cells under defined conditions. Stem Cells 28(10):1893–1904.  https://doi.org/10.1002/stem.499 CrossRefPubMedPubMedCentralGoogle Scholar
  87. Tada M, Takahama Y, Abe K, Nakatsuji N, Tada T (2001) Nuclear reprogramming of somatic cells by in vitro hybridization with ES cells. Curr Biol 11(19):1553–1558.  https://doi.org/10.1016/S0960-9822(01)00459-6 CrossRefPubMedGoogle Scholar
  88. 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 CrossRefPubMedGoogle Scholar
  89. Takahashi K, Okita K, Nakagawa M, Yamanaka S (2007a) Induction of pluripotent stem cells from fibroblast cultures. Nat Protoc 2(12):3081–3089.  https://doi.org/10.1038/nprot.2007.418 CrossRefPubMedGoogle Scholar
  90. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007b) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131(5):861–872.  https://doi.org/10.1016/j.cell.2007.11.019 CrossRefPubMedGoogle Scholar
  91. Thomson JA, Itskovitz-eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM (1998) Embryonic stem cell lines derived from human blastocysts. Sci Rep 282:1145–1147.  https://doi.org/10.1126/science.282.5391.1145 CrossRefGoogle Scholar
  92. Trabucchi M, Briata P, Garcia-Mayoral M, Haase AD, Filipowicz W, Ramos A et al (2009) The RNA-binding protein KSRP promotes the biogenesis of a subset of microRNAs. Nature 459(7249):1010–1014.  https://doi.org/10.1038/nature08025 CrossRefPubMedPubMedCentralGoogle Scholar
  93. Walker JM (2009) Neurodegeneration. Life Sci 531.  https://doi.org/10.1007/978-1-62703-239-1_1
  94. Wang G, McCain ML, Yang L, He A, Pasqualini FS, Agarwal A et al (2014) Modeling the mitochondrial cardiomyopathy of Barth syndrome with induced pluripotent stem cell and heart-on-chip technologies. Nat Med 20(6):616–623.  https://doi.org/10.1038/nm.3545 CrossRefPubMedPubMedCentralGoogle Scholar
  95. Wang B, Zhao M-Z, Cui N-P, Lin D-D, Zhang A-Y, Qin Y et al (2015) Krüppel-like factor 4 induces apoptosis and inhibits tumorigenic progression in SK-BR-3 breast cancer cells. FEBS Open Bio 5:147–154.  https://doi.org/10.1016/j.fob.2015.02.003 CrossRefPubMedPubMedCentralGoogle Scholar
  96. Warren L, Manos PD, Ahfeldt T, Loh Y, Li H, Daley Q et al (2010) Highly efficient reprogramming to pluripotency and directed differentiation of human cells using synthetic modified mRNA Luigi. Cell Stem Cell 7(5):618–630.  https://doi.org/10.1016/j.stem.2010.08.012.Highly CrossRefPubMedPubMedCentralGoogle Scholar
  97. Wernig M, Meissner A, Foreman R, Brambrink T, Ku M, Hochedlinger K et al (2007) In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature 448(7151):318–324.  https://doi.org/10.1038/nature05944 CrossRefPubMedGoogle Scholar
  98. Wernig M, Zhao J-P, Pruszak J, Hedlund E, Fu D, Soldner F et al (2008) Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson’s disease. Proc Natl Acad Sci 105(15):5856–5861.  https://doi.org/10.1073/pnas.0801677105 CrossRefPubMedGoogle Scholar
  99. Whitlock NC (2012) Resveratrol-induced apoptosis is mediated by early growth Response-1, Krüppel-like factor 4, and activating transcription factor 3. Cancer Prev Res 4(1):116–127.  https://doi.org/10.1158/1940-6207.CAPR-10-0218.Resveratrol-induced CrossRefGoogle Scholar
  100. Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KHS (1997) Viable offspring derived from fetal and adult mammalian cells. Cloning Stem Cells 9(1):3–7.  https://doi.org/10.1089/clo.2006.0002 CrossRefGoogle Scholar
  101. Yagi T, Ito D, Okada Y, Akamatsu W, Nihei Y, Yoshizaki T et al (2011) Modeling familial Alzheimer’s disease with induced pluripotent stem cells. Hum Mol Genet 20(23):4530–4539.  https://doi.org/10.1093/hmg/ddr394 CrossRefPubMedGoogle Scholar
  102. Yang DH, Moss EG (2003) Temporally regulated expression of Lin-28 in diverse tissues of the developing mouse. Gene Expr Patterns 3(6):719–726.  https://doi.org/10.1016/S1567-133X(03)00140-6 CrossRefPubMedGoogle Scholar
  103. Ye L, Chang YH, Xiong Q, Zhang P, Zhang L, Somasundaram P et al (2014) Cardiac repair in a porcine model of acute myocardial infarction with human induced pluripotent stem cell-derived cardiovascular cells. Cell Stem Cell 15(6):750–761.  https://doi.org/10.1016/j.stem.2014.11.009 CrossRefPubMedPubMedCentralGoogle Scholar
  104. Yet S, Nulty MMM, Folta SC, Yen H, Yoshizumi M, Hsieh C et al (1998) Human EZF, a Krüppel-like zinc finger protein, is expressed in vascular endothelial cells and contains transcriptional activation and repression domains. J Biol Chem 273(2):1026–1031CrossRefPubMedGoogle Scholar
  105. Yong-Wook J, Hysolli E, Kim K-Y, Tanaka Y, Park I-H (2012) Human induced pluripotent stem cells and neurodegenerative disease: prospects for novel therapies. Curr Opin Neurol 25(2):125–130.  https://doi.org/10.1097/WCO.0b013e3283518226.Human CrossRefGoogle Scholar
  106. Yoon HS, Yang VW (2004) Requirement of Krüppel-like factor 4 in preventing entry into mitosis following DNA damage. J Biol Chem 279(6):5035–5041.  https://doi.org/10.1074/jbc.M307631200 CrossRefPubMedGoogle Scholar
  107. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S et al (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318(5858):1917–1920.  https://doi.org/10.1126/science.1151526 CrossRefPubMedGoogle Scholar
  108. Zafarana G, Avery SR, Avery K, Moore HD, Andrews PW (2009) Specific knockdown of OCT4 in human embryonic stem cells by inducible short hairpin RNA interference. Stem Cells 27(4):776–782.  https://doi.org/10.1002/stem.5 CrossRefPubMedPubMedCentralGoogle Scholar
  109. Zhao S, Nichols J, Smith AG, Li M (2004) SoxB transcription factors specify neuroectodermal lineage choice in ES cells. Mol Cell Neurosci 27(3):332–342.  https://doi.org/10.1016/j.mcn.2004.08.002 CrossRefPubMedGoogle Scholar
  110. Zhao S, Jiang E, Chen S, Gu Y, Shangguan AJ, Lv T et al (2016) PiggyBac transposon vectors: the tools of the human gene encoding. Translational Lung Cancer Res 5(1):120–125.  https://doi.org/10.3978/j.issn.2218-6751.2016.01.05 CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Chavali Kavyasudha
    • 1
  • Dannie Macrin
    • 1
  • K. N. ArulJothi
    • 1
  • Joel P. Joseph
    • 1
  • M. K. Harishankar
    • 1
  • Arikketh Devi
    • 1
    Email author
  1. 1.Department of Genetic EngineeringSRM Institute of Science and TechnologyChennaiIndia

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