Back
 JBiSE  Vol.9 No.4 , March 2016
Induced Pluripotent Stem Cells: Next Generation Cells for Tissue Regeneration
Abstract: More than two decades of in vitro experimentation supported by the data from experimental animal studies in both small as well as large experimental animal models have culminated into multiple clinical studies worldwide to assess their regenerative potential. Although the data generated from these studies have only met with cautious response from the researchers, efforts are still underway with the hope to refine the different aspects of cell-based therapy approach to develop it into an effective routine therapeutic intervention. Besides others, search for a cell type with optimal characteristics remains an area of intense research. Pluripotent stem cells in general, and induced pluripotent stem cells in particular have gained special attention of researchers due to their ability to adopt a morphofuntionally competent phenotype. They are being considered as surrogate embryonic stem cells albeit without moral and ethical issues of availability and having better immunological acceptability. We provide a head-to-head comparison of ESCs and iPSCs and an overview of stem cell therapy approach converging on the observed advantages of pluripotent stem cells during pre-clinical and clinical studies.
Cite this paper: Ibrahim, A. , Mehdi, M. , Abbas, A. , Alashkar, A. and Haider, K. (2016) Induced Pluripotent Stem Cells: Next Generation Cells for Tissue Regeneration. Journal of Biomedical Science and Engineering, 9, 226-244. doi: 10.4236/jbise.2016.94017.
References

[1]   Daar, A.S. and Greenwood, H.L. (2007) A Proposed Definition of Regenerative Medicine. Journal of Tissue Engineering and Regenerative Medicine, 1, 179-184.
http://dx.doi.org/10.1002/term.20

[2]   Handberg-Thorsager, M., Fernandez, E. and Salo, E. (2008) Stem Cells and Regeneration in Planarians. Frontiers in Bioscience, 13, 6374-6394.
http://dx.doi.org/10.2741/3160

[3]   Bajada, S., Mazakova, I., Richardson, J.B. and Ashammakhi, N. (2008) Updates on Stem Cells and Their Applications in Regenerative Medicine. Journal of Tissue Engineering and Regenerative Medicine, 2, 169-183.
http://dx.doi.org/10.1002/term.83

[4]   David, B.G., Okamoto, K., Kakizuka, T., Ichimura, T., Watanabe, T.M. and Fujita, H. (2015) Gene Dynamics of Core Transcription Factors for Pluripotency in Embryonic Stem Cells. Journal of Bioscience and Bioengineering, 119, 406-409.
http://dx.doi.org/10.1016/j.jbiosc.2014.09.011

[5]   Alison, M.R., Poulsom, R., Forbes, S. and Wright, N.A. (2002) An Introduction to Stem Cells. Journal of Pathology, 197, 419-423.
http://dx.doi.org/10.1002/path.1187

[6]   Kumar, R., Sharma, A., Pattnaik, A.K. and Varadwaj, P.K. (2010) Stem Cells: An Overview with Respect to Cardiovascular and Renal Disease. Journal of Natural Science, Biology and Medicine, 1, 43-52.
http://dx.doi.org/10.4103/0976-9668.71674

[7]   Jahagirdar, B.N. and Verfaillie, C.M. (2005) Multipotent Adult Progenitor Cell and Stem Cell Plasticity. Stem Cell Reviews, 1, 53-59.
http://dx.doi.org/10.1385/SCR:1:1:053

[8]   Takahashi, K. and Yamanaka, S. (2006) Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors. Cell, 126, 663-676.
http://dx.doi.org/10.1016/j.cell.2006.07.024

[9]   Yu, J., Vodyanik, M.A., Smuga-Otto, K., et al. (2007) Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells. Science, 318, 1917-1920.
http://dx.doi.org/10.1126/science.1151526

[10]   Nakagawa, M., Koyanagi, M., Tanabe, K., et al. (2008) Generation of Induced Pluripotent Stem Cells without Myc from Mouse and Human Fibroblasts. Nature Biotechnology, 26, 101-106.
http://dx.doi.org/10.1038/nbt1374

[11]   Kim, J.B., Zaehres, H., Wu, G., et al. (2008) Pluripotent Stem Cells Induced from Adult Neural Stem Cells by Reprogramming with Two Factors. Nature, 454, 646-650.
http://dx.doi.org/10.1038/nature07061

[12]   Hester, M.E., Song, S., Miranda, C.J., Eagle, A., Schwartz, P.H. and Kaspar, B.K. (2009) Two Factor Reprogramming of Human Neural Stem Cells into Pluripotency. PLoS ONE, 4, e7044.
http://dx.doi.org/10.1371/journal.pone.0007044

[13]   Nemajerova, A., Kim, S.Y., Petrenko, O. and Moll, U.M. (2012) Two-Factor Reprogramming of Somatic Cells to Pluripotent Stem Cells Reveals Partial Functional Redundancy of Sox2 and Klf4. Cell Death & Differentiation, 19, 1268-1276.
http://dx.doi.org/10.1038/cdd.2012.45

[14]   Okita, K., Nakagawa, M., Hyenjong, H., Ichisaka, T. and Yamanaka, S. (2008) Generation of Mouse Induced Pluripotent Stem Cells without Viral Vectors. Science, 322, 949-953.
http://dx.doi.org/10.1126/science.1164270

[15]   Zhou, W. and Freed, C.R. (2009) Adenovi-ral Gene Delivery Can Reprogram Human Fibroblasts to Induced Pluripotent Stem Cells. Stem Cells (Dayton, Ohio), 27, 2667-2674.
http://dx.doi.org/10.1002/stem.201

[16]   Woltjen, K., Michael, I.P., Mohseni, P., et al. (2009) piggyBac Transposition Reprograms Fibroblasts to Induced Pluripotent Stem Cells. Nature, 458, 766-770.
http://dx.doi.org/10.1038/nature07863

[17]   Fontes, A., Macarthur, C.C., Lieu, P.T. and Vemuri, M.C. (2013) Generation of Human-Induced Pluripotent Stem Cells (hiPSCs) Using Episomal Vectors on Defined Essential 8TM Medium Conditions. Methods in Molecular Biology (Clifton, NJ.), 997, 57-72.
http://dx.doi.org/10.1007/978-1-62703-348-0_6

[18]   Hu, K. and Slukvin, I. (2013) Generation of Transgene-Free iPSC Lines from Human Normal and Neoplastic Blood Cells Using Epi-somal Vectors. Methods in Molecular Biology (Clifton, NJ.), 997, 163-176.
http://dx.doi.org/10.1007/978-1-62703-348-0_13

[19]   Meraviglia, V., Zanon, A., Lavdas, A.A., et al. (2015) Generation of Induced Pluripotent Stem Cells from Frozen Buffy Coats Using Non-Integrating Episomal Plasmids. Journal of Visualized Experiments, 100, e52885.
http://dx.doi.org/10.3791/52885

[20]   Hoffman, L.M. and Carpenter, M.K. (2005) Characteri-zation and Culture of Human Embryonic Stem Cells. Nature Biotechnology, 23, 699-708.
http://dx.doi.org/10.1038/nbt1102

[21]   Martin, G.R. (1981) Isolation of a Pluripotent Cell Line from Early Mouse Embryos Cultured in Medium Conditioned by Teratocarcinoma Stem Cells. Proceedings of the National Academy of Sciences of the United States of America, 78, 7634-7638.
http://dx.doi.org/10.1073/pnas.78.12.7634

[22]   Thomson, J.A., Itskovitz-Eldor, J., Shapiro, S.S., et al. (1998) Embryonic Stem Cell Lines Derived from Human Blastocysts. Science, 282, 1145-1147.
http://dx.doi.org/10.1126/science.282.5391.1145

[23]   Cowan, C.A., Klimanskaya, I., McMahon, J., et al. (2004) Derivation of Embryonic Stem-Cell Lines from Human Blastocysts. The New England Journal of Medicine, 350, 1353-1356.
http://dx.doi.org/10.1056/NEJMsr040330

[24]   Strom, S., Inzunza, J., Grinnemo, K.-H., et al. (2007) Me-chanical Isolation of the Inner Cell Mass Is Effective In Derivation of New Human Embryonic Stem Cell Lines. Human Reproduction, 22, 3051-3058.
http://dx.doi.org/10.1093/humrep/dem335

[25]   Draper, J.S., Smith, K., Gokhale, P., et al. (2004) Recurrent Gain of Chromosomes 17q and 12 in Cultured Human Embryonic Stem Cells. Nature Biotechnology, 22, 53-54.
http://dx.doi.org/10.1038/nbt922

[26]   Brimble, S.N., Zeng, X., Weiler, D.A., et al. (2004) Karyotypic Stability, Genotyping, Differentiation, Feeder-Free Maintenance, and Gene Expression Sampling in Three Human Embryonic Stem Cell Lines Derived Prior to August 9, 2001. Stem Cells and Development, 13, 585-597.
http://dx.doi.org/10.1089/scd.2004.13.585

[27]   Mitalipova, M.M., Rao, R.R., Hoyer, D.M., et al. (2005) Preserving the Genetic Integrity of Human Embryonic Stem Cells. Nature Biotechnology, 23, 19-20.
http://dx.doi.org/10.1038/nbt0105-19

[28]   Turetsky, T., Aizenman, E., Gil, Y., et al. (2008) Laser-Assisted Derivation of Human Embryonic Stem Cell Lines from IVF Embryos after Preimplantation Genetic Diagnosis. Human Reproduction, 23, 46-53.
http://dx.doi.org/10.1093/humrep/dem351

[29]   Ginis, I., Luo, Y., Miura, T., et al. (2004) Differences between Human and Mouse Embryonic Stem Cells. Developmental Biology, 269, 360-380.
http://dx.doi.org/10.1016/j.ydbio.2003.12.034

[30]   Burdon, T., Smith, A. and Savatier, P. (2002) Signalling, Cell Cycle and Pluripotency in Embryonic Stem Cells. Trends in Cell Biology, 12, 432-438.
http://dx.doi.org/10.1016/S0962-8924(02)02352-8

[31]   Dani, C., Chambers, I., Johnstone, S., et al. (1998) Paracrine Induction of Stem Cell Renewal by LIF-Deficient Cells: A New ES Cell Regulatory Pathway. Developmental Biology, 203, 149-162.
http://dx.doi.org/10.1006/dbio.1998.9026

[32]   Chambers, I., Colby, D., Robertson, M., et al. (2003) Functional Expression Cloning of Nanog, a Pluripotency Sustaining Factor in Embryonic Stem Cells. Cell, 113, 643-655.
http://dx.doi.org/10.1016/S0092-8674(03)00392-1

[33]   Blancas, A.A., Chen, C.-S., Stolberg, S. and McCloskey, K.E. (2011) Adhesive Forces in Embryonic Stem Cell Cultures. Cell Adhesion & Migration, 5, 472-479.
http://dx.doi.org/10.4161/cam.5.6.18270

[34]   Amit, M., Margulets, V., Segev, H., et al. (2003) Human Feeder Layers for Human Embryonic Stem Cells. Biology of Reproduction, 68, 2150-2156.
http://dx.doi.org/10.1095/biolreprod.102.012583

[35]   Richards, M., Fong, C.-Y., Chan, W.-K., Wong, P.-C. and Bong-so, A. (2002) Human Feeders Support Prolonged Undifferentiated Growth of Human Inner Cell Masses and Embryonic Stem Cells. Nature Biotechnology, 20, 933-936.
http://dx.doi.org/10.1038/nbt726

[36]   Miyamoto, K., Hayashi, K., Suzuki, T., et al. (2004) Human Placenta Feeder Layers Support Undifferentiated Growth of Primate Embryonic Stem Cells. Stem Cells, 22, 433-440.
http://dx.doi.org/10.1634/stemcells.22-4-433

[37]   Cheng, L., Hammond, H., Ye, Z., Zhan, X. and Dravid, G. (2003) Human Adult Marrow Cells Support Prolonged Expansion of Human Embryonic Stem Cells in Culture. Stem Cells, 21, 131-142.
http://dx.doi.org/10.1634/stemcells.21-2-131

[38]   Bongso, A., Fong, C.-Y., Ng, S.-C. and Ratnam, S. (1994) Fertilization and Early Embryology: Isolation and Culture of Inner Cell Mass Cells from Human Blastocysts. Human Reproduction, 9, 2110-2117.

[39]   Gerecht, S., Burdick, J.A., Ferreira, L.S., Townsend, S.A., Langer, R. and Vun-jak-Novakovic, G. (2007) Hyaluronic Acid Hydrogel for Controlled Self-Renewal and Differentiation of Human Embryonic Stem Cells. Proceedings of the National Academy of Sciences of the United States of America, 104, 11298-11303.
http://dx.doi.org/10.1073/pnas.0703723104

[40]   Kristensen, D.M., Kalisz, M. and Nielsen, J.H. (2005) Cytokine Signalling in Embryonic Stem Cells. APMIS, 113, 756-772.
http://dx.doi.org/10.1111/j.1600-0463.2005.apm_391.x

[41]   Dahéron, L., Opitz, S.L., Zaehres, H., et al. (2004) LIF/STAT3 Signaling Fails to Maintain Self-Renewal of Human Embryonic Stem Cells. Stem Cells, 22, 770-778.
http://dx.doi.org/10.1634/stemcells.22-5-770

[42]   Suter, D.M. and Krause, K.-H. (2008) Neural Commitment of Embryonic Stem Cells: Molecules, Pathways and Potential for Cell Therapy. The Journal of Pathology, 215, 355-368.
http://dx.doi.org/10.1002/path.2380

[43]   Parsons, X.H. (2012) MicroRNA Profiling Reveals Distinct Mechanisms Governing Cardiac and Neural Lineage-Specification of Pluripotent Human Embryonic Stem Cells. Journal of Stem Cell Research & Therapy, 2, 124.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3554249/

[44]   Parsons, X.H., Teng, Y.D., Parsons, J.F., Snyder, E.Y., Smotrich, D.B. and Moore, D.A. (2011) Efficient Derivation of Human Cardiac Precursors and Cardiomyocytes from Pluripotent Human Embryonic Stem Cells with Small Molecule Induction. Journal of Visualized Exper-iments (JoVE), No. 57, e3274.

[45]   Vassena, R., Eguizabal, C., Heindryckx, B., et al. (2015) Stem Cells in Reproductive Medicine: Ready for the Patient? Human Reproduction, 30, 2014-2021.
http://dx.doi.org/10.1093/humrep/dev181

[46]   Lo, B. and Parham, L. (2009) Ethical Issues in Stem Cell Research. Endocrine Reviews, 30, 204-213.
http://dx.doi.org/10.1210/er.2008-0031

[47]   Baker, D.E.C., Harrison, N.J., Maltby, E., et al. (2007) Adaptation to Culture of Human Embryonic Stem Cells and Oncogenesis in Vivo. Nature Biotechnology, 25, 207-215.
http://dx.doi.org/10.1038/nbt1285

[48]   Tan, Y., Ooi, S. and Wang, L. (2014) Immunogenicity and Tumorigenicity of Pluripotent Stem Cells and Their Derivatives: Genetic and Epigenetic Perspectives. Current Stem Cell Research & Therapy, 9, 63-72.
http://dx.doi.org/10.2174/1574888X113086660068

[49]   Swijnenburg, R.-J., Tanaka, M., Vogel, H., et al. (2005) Embryonic Stem Cell Immunogenicity Increases upon Differentiation after Transplantation into Ischemic Myocardium. Circulation, 112, I166-I172.

[50]   Ladhoff, J., Bader, M., Brosel, S., et al. (2009) Low Immunogenicity of Endothelial Derivatives from Rat Embryonic Stem Cell-Like Cells. Cell Research, 19, 507-518.
http://dx.doi.org/10.1038/cr.2009.21

[51]   Sánchez, L., Gutierrez-Aranda, I., Ligero, G., et al. (2011) Enrichment of Human ESC-Derived Multipotent Mesenchymal Stem Cells with Immunosuppressive and Anti-Inflammatory Properties Capable to Protect Against Experimental Inflammatory Bowel Disease. Stem Cells, 29, 251-262.
http://dx.doi.org/10.1002/stem.569

[52]   Lee, A.S., Tang, C., Rao, M.S., Weissman, I.L. and Wu, J.C. (2013) Tumor-igenicity as a Clinical Hurdle for Pluripotent Stem Cell Therapies. Nature Medicine, 19, 998-1004.
http://dx.doi.org/10.1038/nm.3267

[53]   Knoepfler, P.S. (2009) Deconstructing Stem Cell Tumorigenicity: A Roadmap to Safe Regenerative Medicine. Stem Cells, 27, 1050-1056.
http://dx.doi.org/10.1002/stem.37

[54]   Murugan, V. (2009) Embryonic Stem Cell Research: A Decade of Debate from Bush to Obama. Yale Journal of Biology and Medicine, 82, 101-103.

[55]   Kington, R.S. (2009) Guidelines on Human Stem Cell Research. Stem Cell Information, NIH.

[56]   Puri, M.C. and Nagy, A. (2012) Concise Review: Embryonic Stem Cells versus Induced Pluripotent Stem Cells: The Game Is on. Stem Cells, 30, 10-14.
http://dx.doi.org/10.1002/stem.788

[57]   Wilmut, I., Schnieke, A.E., McWhir, J., Kind, A.J. and Camp-bell, K.H.S. (1997) Viable Offspring Derived from Fetal and Adult Mammalian Cells. Nature, 385, 810-813.
http://dx.doi.org/10.1038/385810a0

[58]   Polo, J.M., Liu, S., Figueroa, M.E., et al. (2010) Cell Type of Origin Influences the Molecular and Functional Properties of Mouse Induced Pluripotent Stem Cells. Nature Biotechnology, 28, 848-855.
http://dx.doi.org/10.1038/nbt.1667

[59]   Chin, M.H., Mason, M.J., Xie, W., et al. (2009) Induced Pluripotent Stem Cells and Embryonic Stem Cells Are Distinguished by Gene Expression Signatures. Cell Stem Cell, 5, 111-123.
http://dx.doi.org/10.1016/j.stem.2009.06.008

[60]   Zhao, T., Zhang, Z.-N., Rong, Z. and Xu, Y. (2011) Immunogenicity of Induced Pluripotent Stem Cells. Nature, 474, 212-215.
http://dx.doi.org/10.1038/nature10135

[61]   Takahashi, K., Tanabe, K., Ohnuki, M., et al. (2007) Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors. Cell, 131, 861-872.
http://dx.doi.org/10.1016/j.cell.2007.11.019

[62]   Stadtfeld, M., Nagaya, M., Utikal, J., Weir, G. and Hochedlinger, K. (2008) Induced Pluripotent Stem Cells Generated without Viral Integration. Science, 322, 945-949.
http://dx.doi.org/10.1126/science.1162494

[63]   Yamanaka, S. (2009) Elite and Stochastic Models for Induced Pluripotent Stem Cell Generation. Nature, 460, 49-52.
http://dx.doi.org/10.1038/nature08180

[64]   Tamaoki, N., Takahashi, K., Tanaka, T., et al. (2010) Dental Pulp Cells for Induced Pluripotent Stem Cell Banking. Journal of Dental Research, 89, 773-778.
http://dx.doi.org/10.1177/0022034510366846

[65]   Loh, Y.-H., Agarwal, S., Park, I.-H., et al. (2009) Genera-tion of Induced Pluripotent Stem Cells from Human Blood. Blood, 113, 5476-5479.
http://dx.doi.org/10.1182/blood-2009-02-204800

[66]   Seki, T., Yuasa, S., Oda, M., et al. (2010) Generation of Induced Pluripotent Stem Cells from Human Terminally Differentiated Circulating T Cells. Cell Stem Cell, 7, 11-14.
http://dx.doi.org/10.1016/j.stem.2010.06.003

[67]   Buccini, S., Haider, K.H., Ahmed, R.P.H., Jiang, S. and Ashraf, M. (2012) Cardiac Progenitors Derived from Reprogrammed Mesenchymal Stem Cells Contribute to Angiomyogenic Repair of the Infarcted Heart. Basic Research in Cardiology, 107, 301.
http://dx.doi.org/10.1007/s00395-012-0301-5

[68]   Ahmed, R.P.H., Haider, H.K., Buccini, S., Li, L., Jiang, S. and Ashraf, M. (2011) Reprogramming of Skeletal Myoblasts for Induction of Pluripotency for Tumor-Free Cardiomyogenesis in the Infarcted Heart. Circulation Research, 109, 60-70.
http://dx.doi.org/10.1161/CIRCRESAHA.110.240010

[69]   Wakao, S., Kitada, M., Kuroda, Y., et al. (2011) Multilineage-Differentiating Stress-Enduring (Muse) Cells Are a Primary Source of Induced Pluripotent Stem Cells in Human Fibro-blasts. Proceedings of the National Academy of Sciences of the United States of America, 108, 9875-9880.
http://dx.doi.org/10.1073/pnas.1100816108

[70]   Li, Y., Shen, Z., Shelat, H. and Geng, Y.-J. (2013) Reprogramming Somatic Cells to Pluripotency: A Fresh Look at Yamanaka’s Model. Cell Cycle, 12, 3594-3598.
http://dx.doi.org/10.4161/cc.26952

[71]   Buganim, Y., Faddah, D.A., Cheng, A.W., et al. (2012) Single-Cell Expression Analyses during Cellular Reprogramming Reveal an Early Stochastic and a Late Hierarchic Phase. Cell, 150, 1209-1222.
http://dx.doi.org/10.1016/j.cell.2012.08.023

[72]   Yamanaka, S. (2007) Strategies and New Developments in the Generation of Patient-Specific Pluripotent Stem Cells. Cell Stem Cell, 1, 39-49.
http://dx.doi.org/10.1016/j.stem.2007.05.012

[73]   Wernig, M., Meissner, A., Foreman, R., et al. (2007) In Vitro Reprogramming of Fibroblasts into a Pluripotent ES- Cell-Like State. Nature, 448, 318-324.
http://dx.doi.org/10.1038/nature05944

[74]   Wernig, M., Meissner, A., Cassady, J.P. and Jaenisch, R. (2008) c-Myc Is Dispensable for Direct Reprogramming of Mouse Fibroblasts. Cell Stem Cell, 2, 10-12.
http://dx.doi.org/10.1016/j.stem.2007.12.001

[75]   Huangfu, D., Osafune, K., Maehr, R., et al. (2008) Induction of Pluripotent Stem Cells from Primary Human Fibroblasts with Only Oct4 and Sox2. Nature Biotechnology, 26, 1269-1275.
http://dx.doi.org/10.1038/nbt.1502

[76]   Kim, J.B., Greber, B., Araúzo-Bravo, M.J., et al. (2009) Direct Reprogramming of Human Neural Stem Cells by OCT4. Nature, 461, 649-653.
http://dx.doi.org/10.1038/nature08436

[77]   Tsai, S.-Y., Bouwman, B.A., Ang, Y.-S., et al. (2011) Single Transcription Factor Reprogramming of Hair Follicle Dermal Papilla Cells to Induced Pluripotent Stem Cells. Stem Cells, 29, 964-971.
http://dx.doi.org/10.1002/stem.649

[78]   Zhu, S., Li, W., Zhou, H., et al. (2010) Reprogramming of Human Primary Somatic Cells by OCT4 and Chemical Compounds. Cell Stem Cell, 7, 651-655.
http://dx.doi.org/10.1016/j.stem.2010.11.015

[79]   Lyssiotis, C.A., Foreman, R.K., Staerk, J., et al. (2009) Reprogramming of Murine Fibroblasts to Induced Pluripotent Stem Cells with Chemical Complementation of Klf4. Proceedings of the National Academy of Sciences of the United States of America, 106, 8912-8917.
http://dx.doi.org/10.1073/pnas.0903860106

[80]   Feng, B., Ng, J.-H., Heng, J.-C.D. and Ng, H.-H. (2009) Molecules That Promote or Enhance Reprogramming of Somatic Cells to Induced Pluripotent Stem Cells. Cell Stem Cell, 4, 301-312.
http://dx.doi.org/10.1016/j.stem.2009.03.005

[81]   Yamaguchi, T., Hamanaka, S. and Nakauchi, H. (2014) The Generation and Maintenance of Rat Induced Pluripotent Stem Cells. In: Kioussi, C., Ed., Stem Cells and Tissue Repair. Methods in Molecular Biology, Vol. 1210, Springer, New York, 143-150.
http://dx.doi.org/10.1007/978-1-4939-1435-7_11

[82]   Merkl, C., Saalfrank, A., Riesen, N., et al. (2013) Efficient Generation of Rat Induced Pluripotent Stem Cells Using a Non-Viral Inducible Vector. PLoS ONE, 8, e55170.
http://dx.doi.org/10.1371/journal.pone.0055170

[83]   Fang, R., Liu, K., Zhao, Y., et al. (2014) Generation of Naive Induced Pluripotent Stem Cells from Rhesus Monkey Fibroblasts. Cell Stem Cell, 15, 488-496.
http://dx.doi.org/10.1016/j.stem.2014.09.004

[84]   Wu, Z., Chen, J., Ren, J., et al. (2009) Generation of Pig Induced Pluripotent Stem Cells with a Drug-Inducible System. Journal of Molecular Cell Biology, 1, 46-54.
http://dx.doi.org/10.1093/jmcb/mjp003

[85]   Ezashi, T., Telugu, B.P.V.L., Alexenko, A.P., Sachdev, S., Sinha, S. and Roberts, R.M. (2009) Derivation of Induced Pluripotent Stem Cells from Pig Somatic Cells. Proceedings of the National Academy of Sciences of the United States of America, 106, 10993-10998.
http://dx.doi.org/10.1073/pnas.0905284106

[86]   Park, I.-H., Zhao, R., West, J.A., et al. (2008) Reprogramming of Human Somatic Cells to Pluripotency with Defined Factors. Nature, 451, 141-146.
http://dx.doi.org/10.1038/nature06534

[87]   Aasen, T., Raya, A., Barrero, M.J., et al. (2008) Efficient and Rapid Generation of Induced Pluripotent Stem Cells from Human Keratinocytes. Nature Biotechnology, 26, 1276-1284.
http://dx.doi.org/10.1038/nbt.1503

[88]   Aoi, T., Yae, K., Nakagawa, M., et al. (2008) Generation of Pluripotent Stem Cells from Adult Mouse Liver and Stomach Cells. Science, 321, 699-702.
http://dx.doi.org/10.1126/science.1154884

[89]   Eminli, S., Foudi, A., Stadtfeld, M., et al. (2009) Differentiation Stage Determines Reprogramming Potential of Hematopoietic Cells into Induced Pluripotent Stem Cells. Nat Genet, 41, 968-976.
http://dx.doi.org/10.1038/ng.428

[90]   Eminli, S., Utikal, J., Arnold, K., Jaenisch, R. and Hochedlinger, K. (2008) Reprogramming of Neural Progenitor Cells into Induced Pluripotent Stem Cells in the Absence of Exogenous Sox2 Expression. Stem Cells, 26, 2467-2474.
http://dx.doi.org/10.1634/stemcells.2008-0317

[91]   Shao, L. and Wu, W.-S. (2010) Gene-Delivery Systems for iPS Cell Generation. Expert Opinion on Biological Therapy, 10, 231-242.
http://dx.doi.org/10.1517/14712590903455989

[92]   Soldner, F., Hockemeyer, D., Beard, C., et al. (2009) Parkinson’s Disease Patient-Derived Induced Pluripotent Stem Cells Free of Viral Reprogramming Factors. Cell, 136, 964-977.
http://dx.doi.org/10.1016/j.cell.2009.02.013

[93]   Nishimura, K., Sano, M., Ohtaka, M., et al. (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, 4760-4771.
http://dx.doi.org/10.1074/jbc.M110.183780

[94]   Yu, J., Hu, K., Smuga-Otto, K., et al. (2009) Human Induced Pluripotent Stem Cells Free of Vector and Transgene Sequences. Science, 324, 797-801.
http://dx.doi.org/10.1126/science.1172482

[95]   Shi, Y., Do, J.T., Desponts, C., Hahm, H.S., Sch?ler, H.R. and Ding, S. (2008) A Combined Chemical and Genetic Approach for the Generation of Induced Pluripotent Stem Cells. Cell Stem Cell, 2, 525-528.
http://dx.doi.org/10.1016/j.stem.2008.05.011

[96]   Mallanna, S.K. and Rizzino, A. (2010) Emerg-ing Roles of microRNAs in the Control of Embryonic Stem Cells and the Generation of Induced Pluripotent Stem Cells. De-velopmental Biology, 344, 16-25.
http://dx.doi.org/10.1016/j.ydbio.2010.05.014

[97]   Houbaviy, H.B., Murray, M.F. and Sharp, P.A. (2003) Embryonic Stem Cell-Specific MicroRNAs. Developmental Cell, 5, 351-358.
http://dx.doi.org/10.1016/S1534-5807(03)00227-2

[98]   Judson, R.L., Babiarz, J.E., Venere, M. and Blelloch, R. (2009) Embryonic Stem Cell-Specific microRNAs Promote Induced Pluripotency. Nature Biotechnology, 27, 459-461.
http://dx.doi.org/10.1038/nbt.1535

[99]   Anokye-Danso, F., Snitow, M. and Morrisey, E.E. (2012) How microRNAs Facilitate Reprogramming to Pluripotency. Journal of Cell Science, 125, 4179-4187.
http://dx.doi.org/10.1242/jcs.095968

[100]   Miyoshi, N., Ishii, H., Nagano, H., et al. (2011) Reprogramming of Mouse and Human Cells to Pluripotency Using Mature microRNAs. Cell Stem Cell, 8, 633-638.
http://dx.doi.org/10.1016/j.stem.2011.05.001

[101]   Anokye-Danso, F., Trivedi, C.M., Juhr, D., et al. (2011) Highly Efficient miRNA-Mediated Reprogramming of Mouse and Human Somatic Cells to Pluripotency. Cell Stem Cell, 8, 376-388.
http://dx.doi.org/10.1016/j.stem.2011.03.001

[102]   Vitaloni, M., Pulecio, J., Bilic, J., Kuebler, B., Laricchia-Robbio, L. and Izpisua Belmonte, J.C. (2014) MicroRNAs Contribute to Induced Pluripotent Stem Cell Somatic Donor Memory. The Journal of Biological Chemistry, 289, 2084-2098.
http://dx.doi.org/10.1074/jbc.M113.538702

[103]   Narsinh, K.H., Plews, J. and Wu, J.C. (2011) Comparison of Human Induced Pluripotent and Embryonic Stem Cells: Fraternal or Identical Twins? Molecular Therapy, 19, 635-638.
http://dx.doi.org/10.1038/mt.2011.41

[104]   Vaskova, E.A., Stekleneva, A.E., Medvedev, S.P. and Zakian, S.M. (2013) “Epigenetic Memory” Phenomenon in Induced Pluripotent Stem Cells. Acta Naturae, 5, 15-21.

[105]   Liu, L., Luo, G.-Z., Yang, W., et al. (2010) Activation of the Imprinted Dlk1-Dio3 Region Correlates with Pluripotency Levels of Mouse Stem Cells. The Journal of Biological Chemistry, 285, 19483-19490.
http://dx.doi.org/10.1074/jbc.M110.131995

[106]   Liu, P., Chen, S., Li, X., et al. (2013) Low Immunogenicity of Neural Progenitor Cells Differentiated from Induced Pluripotent Stem Cells Derived from Less Immunogenic Somatic Cells. PLoS ONE, 8, e69617.
http://dx.doi.org/10.1371/journal.pone.0069617

[107]   Alberts, B. (2015) Molecular Biology of the Cell. 6th Edition, Garland Science, Taylor and Francis Group, New York.

[108]   Richly, H., Aloia, L. and Di Croce, L. (2011) Roles of the Polycomb Group Proteins in Stem Cells and Cancer. Cell Death & Disease, 2, e204.
http://dx.doi.org/10.1038/cddis.2011.84

[109]   Chamberlain, S.J., Yee, D. and Magnuson, T. (2008) Polycomb Repressive Complex 2 Is Dispensable for Maintenance of Embryonic Stem Cell Pluripotency. Stem Cells, 26, 1496-1505.
http://dx.doi.org/10.1634/stemcells.2008-0102

[110]   Harrison, T.R., Ed. (1962) Harrison’s Principles of Internal Medicine. McGraw-Hill, New York.

[111]   Soldner, F. and Jaenisch, R. (2012) iPSC Disease Modeling. Science, 338, 1155-1156.
http://dx.doi.org/10.1126/science.1227682

[112]   Ebert, A.D. and Svendsen, C.N. (2010) Stem Cell Model of Spinal Muscular Atrophy. JAMA Neurology, 67, 665-669.
http://dx.doi.org/10.1001/archneurol.2010.89

[113]   Ebert, A.D., Yu, J., Rose, F.F., et al. (2009) Induced Pluripotent Stem Cells from a Spinal Muscular Atrophy Patient. Nature, 457, 277-280.
http://dx.doi.org/10.1038/nature07677

[114]   Kim, C. (2014) Disease Modeling and Cell Based Therapy with iPSC: Future Therapeutic Option with Fast and Safe Application. Blood Research, 49, 7-14.
http://dx.doi.org/10.5045/br.2014.49.1.7

[115]   Mercola, M., Colas, A. and Willems, E. (2013) Induced Pluripotent Stem Cells in Cardiovascular Drug Discovery. Circulation Research, 112, 534-548.
http://dx.doi.org/10.1161/CIRCRESAHA.111.250266

[116]   Drawnel, F.M., Boccardo, S., Prummer, M., et al. (2014) Disease Modeling and Phenotypic Drug Screening for Diabetic Cardiomyopathy Using Human Induced Pluripotent Stem Cells. Cell Reports, 9, 810-821.
http://dx.doi.org/10.1016/j.celrep.2014.09.055

[117]   Singh, V.K., Kalsan, M., Kumar, N., Saini, A. and Chandra, R. (2015) Induced Pluripotent Stem Cells: Applications in Regenerative Medicine, Disease Modeling, and Drug Discovery. Frontiers in Cell and Developmental Biology, 3, 2.
http://dx.doi.org/10.3389/fcell.2015.00002

 
 
Top