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In Pursuit of Porcine Pluripotent Stem Cells for Autologous Cell Therapy

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DOI: 10.4236/scd.2014.44012    3,651 Downloads   4,766 Views   Citations


Treatments to repair the human heart following regenerative diseases remain a challenge for medical science. Unlike lower vertebrate species the human heart lacks a regenerative pathway meaning that research has to be focused on cell transplantation. Porcines (Sus scrofa) are excellent models for cardiovascular disease and pluripotent stem cells (PSCs) generated from porcines will provide important clinical insights for cardiac cell therapy. This could open a new avenue of research into degenerative conditions as porcine is a more effective human proxy to work with. However, bona fide PSCs are currently available onlyin rodents (mouse, rat) and primates (monkey, human). Attempts to derivepluripotent stem cells (PSCs) from porcine have been going on for more than two decades with slow progress. Despite the fact that the porcine stem cells are under increasing glare of publicity due to milestone achievements in this area of research. Advances in stem cell technology, especially the genetic engineering, innovative cell culturing and induced pluripotency to generate stem cells has dramatically revolutionized the basic and applied investigations and applications of porcine stem cells. This review attempts to summarize the major signaling pathways involved in maintenance of pluripotency and the state of the art conceptual and technical progress for generating bona fide porcine PSCs.

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The authors declare no conflicts of interest.

Cite this paper

Verma, V. , Mehta, A. , Pal, S. , Kumar, M. , Singh, B. , Kumar, A. and Gautam, S. (2014) In Pursuit of Porcine Pluripotent Stem Cells for Autologous Cell Therapy. Stem Cell Discovery, 4, 107-124. doi: 10.4236/scd.2014.44012.


[1] Nichols, J. and Smith, A. (2009) Naive and Primed Pluripotent States. Cell Stem Cell, 4, 487-492.
[2] Gurdon, J.B., Elsdale, T.R. and Fischberg, M. (1958) Sexually Mature Individuals of Xenopus laevis from the Transplantation of Single Somatic Nuclei. Nature, 182, 64-65.
[3] 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.
[4] Bilic, J. and Belmonte, J.C.I. (2012) Concise Review: Induced Pluripotent Stem Cells Versus Embryonic Stem Cells: Close Enough or Yet Too Far Apart? Stem Cells, 30, 33-41.
[5] Strojek, R.M., Reed, M.A., Hoover, J.L. and Wagner, T.E. (1990) A Method for Cultivating Morphologically Undifferentiated Embryonic Stem Cells from Porcine Blastocysts. Theriogenology, 33, 901-913.
[6] Notarianni, E., Laurie, S., Moor, R.M. and Evans, M.J. (1990) Maintenance and Differentiation in Culture of Pluripotential Embryonic Cell Lines from Pig Blastocysts. Journal of Reproduction Fertility-Supplement, 41, 51-56.
[7] Hall, V. (2008) Porcine Embryonic Stem Cells: A Possible Source for Cell Replacement Therapy. Stem Cell Reviews, 4, 275-282.
[8] Esteban, M.A., Xu, J., Yang, J., Peng, M., Qin, D., Li, D., Jiang, Z., Chen, J., Deng, K., Zhong, M., Cai, J., Lai, L. and Pei, J. (2009) Generation of Induced Pluripotent Stem Cell Lines from Tibetan Miniature pig. The Journal of Biological Chemistry, 284, 17634-17640.
[9] Wu, Z., Chen, J., Ren, J., Bao, L., Liao, J., Cui, C., Rao, L., Li, H., Gu, Y., Dai, H., Zhu, H., Teng, X., Cheng, L. and Xiao, L. (2009) Generation of Pig Induced Pluripotent Stem Cells with a Drug-Inducible System. Journal of Molecular Cell Biology, 1, 46-54.
[10] Ezashi, T., Telugu, V.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 USA, 106, 1099310998.
[11] West, F.D., Uhl, E.W., Liu, Y., Stowe, H., Lu, Y., Yu, P., Gallegos-Cardenas, A., Pratt, S.L. and Stice, S.L. (2011) Brief Report: Chimeric Pigs Produced from Induced Pluripotent Stem Cells Demonstrate Germline Transmission and No Evidence of Tumor Formation in Young Pigs. Stem Cells, 29, 1640-1643.
[12] Nowak-Imialek, M., Kues, W., Carnwath, J.W. and Niemann, H. (2011) Pluripotent Stem Cells and Reprogrammed Cells in Farm Animals. Microscopy and Microanalysis, 17, 474-497.
[13] Brevini, T.A., Pennarossa, G., Attanasio, L., Vanelli, A., Gasparrini, B. and Gandolfi, F. (2010) Culture Conditions and Signalling Networks Promoting the Establishment of Cell Lines from Parthenogenetic and Biparental Pig Embryos. Stem Cell Reviews and Reports, 6, 484-495.
[14] Smith, A.G., Nichols, J., Robertson, M. and Rathjen, P.D. (1992) Differentiation Inhibiting Activity (DIA/LIF) and Mouse Development. Developmental Biology, 151, 339-351.
[15] Niwa, H., Burdon, T., Chambers, I. and Smith, A. (1998) Self-Renewal of Pluripotent Embryonic Stem Cells Is Mediated via Activation of STAT3. Genes Development, 12, 2048-2060.
[16] Matsuda, T., Nakamura, T., Nakao, K., Arai, T., Katsuki, M., Heike, T. and Yokota, T. (1999) STAT3 Activation Is Sufficient to Maintain an Undifferentiated State of Mouse Embryonic Stem Cells. The EMBO Journal, 18, 4261-4269.
[17] Raz, R., Lee, C.K., Cannizzaro, L.A., d’Eustachio, P. and Levy, D.E. (1999) Essential Role of STAT3 for Embryonic Stem Cell Pluripotency. Proceedings of the National Academy of Sciences of the United States of America, 96, 28462851.
[18] Cartwright, P., McLean, C., Sheppard, A., Rivett, D., Jones, K. and Dalton, S. (2005) LIF/STAT3 Controls ES Cell Self-Renewal and Pluripotency by a Myc-Dependent Mechanism. Development, 132, 885-896.
[19] Ying, Q.L., Stavridis, M., Griffiths, D., Li, M. and Smith, A. (2003) Conversion of Embryonic Stem Cells into Neuroectodermal Precursors in Adherent Monoculture. Nature Biotechnology, 21, 183-186.
[20] Winnier, G., Blessing, M., Labosky, P.A. and Hogan, B.L. (1995) Bone Morphogenetic Protein-4 Is Required for Mesoderm Formation and Patterning in the Mouse. Genes Development, 9, 2105-2116.
[21] Thomson, J.A., Kalishman, J., Golos, T.G., Durning, M., Harris, C.P., Becker, R.A. and Hearn, J.P. (1995) Isolation of a Primate Embryonic Stem Cell Line. Proceedings of the National Academy of Sciences of the United States of America, 92, 7844-7848.
[22] Thomson, J.A., Itskovitz-Eldor, J., Shapiro, S.S., Waknitz, M.A., Swiergiel, J.J., Marshall, V.S. and Jones, J.M. (1998) Embryonic Stem Cell Lines Derived from Human Blastocysts. Science, 282, 1145-1147.
[23] Kawahara, Y., Manabe, T., Matsumoto, M., Kajiume, T. and Yuge, L. (2009) LIF-Free Embryonic Stem Cell Culture in Simulated Microgravity. PLoS ONE, 4, e6343.
[24] Humphrey, R.K., Beattie, G.M., Lopez, A.D., Bucay, N., King, C.C., Firpo, M.T., Rose-John, S. and Hayek, A. (2004) Maintenance of Pluripotency in Human Embryonic Stem Cells Is STAT3 Independent. Stem Cells, 22, 522-530.
[25] James, D., Levine, A.J., Besser, D. and Hemmati-Brivanlou, A. (2005) TGFbeta/Activin/Nodal Signaling Is Necessary for the Maintenance of Pluripotency in Human Embryonic Stem Cells. Development, 132, 1273-1282.
[26] Wang, G., Zhang, H., Zhao, Y., Li, J., Cai, J., Wang, P., Meng, S., Feng, J., Miao, C., Ding, M., Li, D. and Deng, H. (2005) Noggin and bFGF Cooperate to Maintain the Pluripotency of Human Embryonic Stem Cells in the Absence of Feeder Layers. Biochemical and Biophysical Research Communications, 330, 934-942.
[27] Xu, C., Rosler, E., Jiang, J., Lebkowski, J.S., Gold, J.D., O’Sullivan, C., Delavan-Boorsma, K., Mok, M., Bronstein, A. and Carpenter, M.K. (2005) Basic Fibroblast Growth Factor Supports Undifferentiated Human Embryonic Stem Cell Growth without Conditioned Medium. Stem Cells, 23, 315-323.
[28] Davidson, K.C., Jamshidi, P., Daly, R., Hearn, M.T., Pera, M.F. and Dottori, M. (2007) Wnt3a Regulates Survival, Expansion, and Maintenance of Neural Progenitors Derived from Human Embryonic Stem Cells. Molecular and Cellular Neuroscience, 36, 408-415.
[29] Dravid, G., Ye, Z., Hammond, H., Chen, G., Pyle, A., Donovan, P., Yu, X. and Cheng, L. (2005) Defining the Role of Wnt/β-Catenin Signaling in the Survival, Proliferation and Self-Renewal of Human Embryonic Stem Cells. Stem Cells, 23, 1489-1501.
[30] Yasuda, S.Y., Tsuneyoshi, N., Sumi, T., Hasegawa, K., Tada, T., Nakatsuji, N. and Suemori, H. (2006) NANOG Maintains Self-Renewal of Primate ES Cells in the Absence of a Feeder Layer. Genes to Cells, 11, 1115-1123.
[31] Ying, Q.L., Wray, J., Nichols, J., Batlle, M.L., Doble, B., Woodgett, J., Cohen, P. and Smith, A. (2008) The Ground State of Embryonic Stem Cell Self-Renewal. Nature, 453, 519-523.
[32] Alberio, R., Croxall, N. and Allegrucci, A. (2010) Pig Epiblast Stem Cells Depend on Activin/Nodal Signaling for Pluripotency and Self-Renewal. Stem Cells and Development, 19, 1627-1636.
[33] Blomberg, L.A., Schreier, L.L. and Talbot, N.C. (2008) Expression Analysis of Pluripotency Factors in the Undifferentiated Porcine Inner Cell Mass and Epiblast During in Vitro Culture. Molecular Reproduction and Development, 75, 450-463.
[34] Hall, V.J., Christensen, J., Gao, Y., Schmidt, M.H. and Hyttel, P. (2009) Porcine Pluripotency Cell Signaling Develops from the Inner Cell Mass to the Epiblast during Early Development. Developmental Dynamics, 238, 2014-2024.
[35] Brevini, T.A., Antonini, S., Pennarossa, G., Maffei, S. and Gandolfi, F. (2012) Pluripotency Network in Porcine Embryos and Derived Cell Lines. Reproduction in Domestic Animals, 47, 86-91.
[36] Welham, M.J., Storm, M.P., Kingham, E. and Bone, H.K. (2007) Phosphoinositide 3-Kinases and Regulation of Embryonic Stem Cell Fate. Biochemical Society Transactions, 35, 225-228.
[37] Mummery, C.L., van Rooyen, M., Bracke, M., van den Eijnden-van Raaij, J., van Zoelen, E.J. and Alitalo, K. (1993) Fibroblast Growth Factor-Mediated Growth Regulation and Receptor Expression in Embryonal Carcinoma and Embryonic Stem Cells and Human Germ Cell Tumours. Biochemical and Biophysical Research Communications, 191, 188-195.
[38] Jirmanova, L., Afanassieff, M., Gobert-Gosse, S., Markossian, S. and Savatier, P. (2002) Differential Contributions of ERK and PI3-Kinase to the Regulation of Cyclin D1 Expression and to the Control of the G1/S Transition in Mouse Embryonic Stem Cells. Oncogene, 21, 5515-5528.
[39] Ma, Y., Yang, J.Y., Cheng, D., Liu, X., Ma, X., West, F.D. and Wang, H. (2014) Comparative Gene Expression Signature of Pig, Human and Mouse Induced Pluripotent Stem Cell Lines Reveals Insight into Pig Pluripotency Gene Networks. Stem Cell Reviews and Reports, 10, 162-176.
[40] Brevini, T.A., Pennarossa, G. and Gandolfi, F. (2010) No Shortcuts to Pig Embryonic Stem Cells. Theriogenology, 74, 544-550.
[41] Piedrahita, J.A., Anderson, G.B. and Bondurant, R.H. (1990) Influence of Feeder Layer Type on the Efficiency of Isolation of Porcine Embryo-Derived Cell Lines. Theriogenology, 34, 865-877.
[42] Evans, M.J., Notarianni, E., Laurie, S. and Moor, R.M. (1990) Derivation and Preliminary Characterization of Pluripotent Cell Lines from Porcine and Bovine Blastocysts. Theriogenology, 33, 125-128.
[43] Piedrahita, J.A., Anderson, G.B. and Bondurant, R.H. (1990) On the Isolation of Embryonic Stem Cells: Comparative Behavior of Murine, Porcine and Ovine Embryos. Theriogenology, 34, 879-901.
[44] Talbot, N.C., Rexroad Jr., C.E., Pursel, V.G. and Powell, A.M. (1993) Alkaline Phosphatase Staining of Pig and Sheep Epiblast Cells in Culture. Molecular Reproduction and Development, 36, 139-147.
[45] Verma, V., Gautam, S.K., Singh, B., Manik, R.S., Palta, P., Singla, S.K., Goswami, S.L. and Chauhan, M.S. (2007) Isolation and Characterization of Embryonic Stem Cell-Like Cells from in Vitro-Produced Buffalo (Bubalus bubalis) Embryos. Molecular Reproduction and Development, 74, 520-529.
[46] Verma, V., Huang, B., Kallingappa, P.K. and Oback, B. (2013) Dual Kinase Inhibition Promotes Pluripotency in Finite Bovine Embryonic Cell Lines. Stem Cells and Development, 22, 1728-1742.
[47] Wheeler, M.B. (1994) Development and Validation of Swine Embryonic Stem Cells: A Review. Reproduction, Fertility and Development, 6, 563-568.
[48] Shim, H., Gutierrez-Adan, A., Chen, L.R., BonDurant, R.H., Behboodi, E. and Anderson, G.B. (1997) Isolation of Pluripotent Stem Cells from Cultured Porcine Primordial Germ Cells. Biology of Reproduction, 57, 1089-1095.
[49] Chen, L.R., Shiue, Y.L., Bertolini, L., Medrano, J.F., BonDurant, R.H. and Anderson, G.B. (1999) Establishment of Pluripotent Cell Lines from Porcine Preimplantation Embryos. Theriogenology, 52, 195-212.
[50] Miyoshi, K., Taguchi, Y., Sendai, Y., Hoshi, H. and Sato, E. (2000) Establishment of a Porcine Cell Line from in Vitro-Produced Blastocysts and Transfer of the Cells into Enucleated Oocytes. Biology of Reproduction, 62, 1640-1646.
[51] Vassiliev, I., Vassilieva, S., Beebe, L.F., Harrison, S.J., McIlfatrick, S.M. and Nottle, M. B. (2010) In Vitro and in Vivo Characterization of Putative Porcine Embryonic Stem Cells. Cellular Reprogramming, 12, 223-230.
[52] Haraguchi, S., Kikuchi, K., Nakai, M. and Tokunaga, T. (2012) Establishment of Self-Renewing Porcine Embryonic Stem Cell-Like Cells by Signal Inhibition. Journal of Reproduction and Development, 58, 707-716.
[53] Buehr, M., Meek, S., Blair, K., Yang, J., Ure, J., Silva, J., McLay, R., Hall, J., Ying, Q.L. and Smith, A. (2008) Capture of Authentic Embryonic Stem Cells from Rat Blastocysts. Cell, 135, 1287-1298.
[54] Li, P., Tong, C., Mehrian-Shai, R., Jia, L., Wu, N., Yan, Y., Maxson, R.E., Schulze, E.N., Song, H., Hsieh, C.L., Pera, M.F. and Ying, Q.L. (2008) Germline Competent Embryonic Stem Cells Derived from Rat Blastocysts. Cell, 135, 1299-1310.
[55] Hanna, J., Cheng, A.W., Saha, K., Kim, J., Lengner, C.J., Soldner, F., Cassady, J.P., Muffat, J., Carey, B.W. and Jaenisch, R. (2010) Human Embryonic Stem Cells with Biological and Epigenetic Characteristics Similar to Those of Mouse ESCs. Proceedings of the National Academy of Sciences of the United States of America, 107, 9222-9227.
[56] Pomp, O., Dreesen, O., Leong, D.F., Meller-Pomp, O., Tan, F., Zhou, T.F. and Colman, A. (2011) Unexpected X Chromosome Skewing during Culture and Reprogramming of Human Somatic Cells Can Be Alleviated by Exogenous Telomerase. Cell Stem Cell, 9, 156-165.
[57] Buecker, C., Chen, H.H., Polo, J.M., Daheron, L., Bu, L., Barakat, T.S., Okwieka, P., Porter, A., Gribnau, J., Hochedlinger, K. and Geijsen, N. (2010) A Murine ESC-Like State Facilitates Transgenesis and Homologous Recombination in Human Pluripotent Stem Cells. Cell Stem Cell, 6, 535-546.
[58] Fujishiro, S.H., Nakano, K., Mizukami, Y., Azami, T., Arai, Y., Matsunari, H., Ishino, R., Nishimura, T., Watanabe, M., Abe, T., Furukawa, Y., Umeyama, K., Yamanaka, S., Ema, M., Nagashima, H. and Hanazono, Y. (2013) Generation of Naive-Like Porcine-Induced Pluripotent Stem Cells Capable of Contributing to Embryonic and Fetal Development. Stem Cells and Development, 22, 473-482.
[59] Kirchhof, N., Carnwath, J.W., Lemme, E., Anastassiadis, K., Scholer, H. and Niemann, H. (2000) Expression Pattern of Oct-4 in Preimplantation Embryos of Different Species. Biology of Reproduction, 63, 1698-1705.
[60] Mitalipov, S.M., Kuo, H.-C., Hennebold, J.D. and Wolf, D.P. (2003) Oct-4 Expression in Pluripotent Cells of the Rhesus Monkey. Biology of Reproduction, 69, 1785-1792.
[61] van Eijk, M.J., van Rooijen, M.A., Modina, S., Scesi, L., Folkers, G., van Tol, H.T., Bevers, M.M., Fisher, S.R., Lewin, H.A., Rakacolli, D., Galli, C., de Vaureix, C., Trounson, A.O., Mummery, C.L. and Gandolfi, F. (1999) Molecular Cloning, Genetic Mapping, and Developmental Expression of Bovine POU5F1. Biology of Reproduction, 60, 1093-1103.
[62] Vejlsted, M., Du, Y., Vajta, G. and Maddox-Hyttel, P. (2006) Post-Hatching Development of the Porcine and Bovine Embryo—Defining Criteria for Expected Development in Vivo and in Vitro. Theriogenology, 65, 153-165.
[63] Wolf, X.A., Rasmussen, M.A., Schauser, K., Jensen, A.T., Schmidt, M. and Hyttel, P. (2011) OCT4 Expression in Outgrowth Colonies Derived from Porcine Inner Cell Masses and Epiblasts. Reproduction in Domestic Animals, 46, 385-392.
[64] du Puy, L., Lopes, S.M., Haagsman, H.P. and Roelen, B.A. (2011) Analysis of Co-Expression of OCT4, NANOG and SOX2 in Pluripotent Cells of the Porcine Embryo, in Vivo and in Vitro. Theriogenology, 75, 513-526.
[65] Silva, J., Nichols, J., Theunissen, T.W., Guo, G., van Oosten, A.L., Barrandon, O., Wray, J., Yamanaka, S., Chambers, I. and Smith, A. (2009) Nanog Is the Gateway to the Pluripotent Ground State. Cell, 138, 722-737.
[66] Nagashima, H., Giannakis, C., Ashman, R.J. and Nottle, M.B. (2004) Sex Differentiation and Germ Cell Production in Chimeric Pigs Produced by Inner Cell Mass Injection into Blastocysts. Biology of Reproduction, 70, 702-707.
[67] Telugu, B.P.V.L., Ezashi, T. and Roberts, R.M. (2010) Porcine Induced Pluripotent Stem Cells Analogous to Naive and Primed Embryonic Stem Cells of the Mouse. The International Journal of Developmental Biology, 54, 1703-1711.
[68] Telugu, B.P.V.L., Ezashi, T., Sinha, S., Alexenko, A.P., Spate, L., Prather, R.S. and Roberts, R.M. (2011) Leukemia Inhibitory Factor (LIF)-Dependent, Pluripotent Stem Cells Established from Inner Cell Mass of Porcine Embryos. The Journal of Biological Chemistry, 286, 28948-28953.
[69] West, F.D., Terlouw, S.L., Kwon, D.J., Mumaw, J.L., Dhara, S.K., Hasneen, K., Dobrinsky, J.R. and Stice, S.L. (2010) Porcine Induced Pluripotent Stem Cells Produce Chimeric Offspring. Stem Cells and Development, 19, 1211-1220.
[70] Park, J.K., Kim, H.S., Uh, K.J., Choi, K.H., Kim, H.M., Lee, T., Yang, B.C., Kim, H.J., Ka, H.H., Kim, H. and Lee, C. K. (2013) Primed Pluripotent Cell Lines Derived from Various Embryonic Origins and Somatic Cells in Pig. PLoS ONE, 8, e52481.
[71] Montserrat, N., de Onate, L., Garreta, E., Gonzalez, F., Adamo, A., Eguizabal, C., Hafner., S, Vassena, R. and Izpisua Belmonte, J.C. (2012) Generation of Feeder-Free Pig Induced Pluripotent Stem Cells without Pou5f1. Cell Transplantation, 21, 815-825.
[72] Cheng, D., Guo, Y., Li, Z., Liu, Y., Gao, X., Gao, Y., Cheng, X., Hu, J. and Wang, W. (2012) Porcine Induced Pluripotent Stem Cells Require LIF and Maintain Their Developmental Potential in Early Stage of Embryos. PLoS ONE, 7, e51778.
[73] Kues Wilfried, A., Herrmann, D., Barg-Kues, B., Haridoss, S., Nowak-Imialek, M., Buchholz, T., Streeck, M., Grebe, A., Grabundzija, I., Merkert, S., Martin, U., Hall, V.J., Rasmussen, M.A., Ivics, Z., Hyttel, P. and Niemann, H. (2013) Derivation and Characterization of Sleeping Beauty Transposon-Mediated Porcine Induced Pluripotent Stem Cells. Stem Cells and Development, 22, 124-135.
[74] Petkov, S., Hyttel, P. and Niemann, H. (2013) The Choice of Expression Vector Promoter Is an Important Factor in the Reprogramming of Porcine Fibroblasts into Induced Pluripotent Cells. Cellular Reprogramming, 15, 1-8.
[75] Strelchenko, N. (1996) Bovine Pluripotent Stem Cells. Theriogenology, 45, 131-140.
[76] Saito, S., Sawai, K., Ugai, H., Moriyasu, S., Minamihashi, A., Yamamoto, Y., Hirayama, H., Kageyama, S., Pan, J., Murata, T., Kobayashi, Y., Obata, Y. and Yokoyama, K.K. (2003) Generation of Cloned Calves and Transgenic Chimeric Embryos from Bovine Embryonic Stem-Like Cells. Biochemical and Biophysical Research Communications, 309, 104-113.
[77] Montserrat, N., Bahima, E.G., Batlle, L., Hafner, S., Rodrigues, A.M., González, F. and Izpisúa Belmonte, J.C. (2013) Generation of Pig iPS Cells: A Model for Cell Therapy. Journal of Cardiovascular Translational Research, 6, 295-297.
[78] Ludwig, T.E., Bergendahl, V., Levenstein, M.E., Yu, J., Probasco, M.D. and Thomson, J.A. (2006) Feeder-Independent Culture of Human Embryonic Stem Cells. Nature Methods, 3, 637-646.
[79] Nichols, J., Jones, K., Phillips, J.M., Newland, S.A., Roode, M., Mansfield, W., Smith, A. and Cooke, A. (2009) Validated Germline-Competent Embryonic Stem Cell Lines from Nonobese Diabetic Mice. Nature Methods, 15, 814-818.
[80] Li, J., Wang, G., Wang, C., Zhao, Y., Zhang, H., Tan, Z., Song, Z., Ding, M. and Deng, H. (2007) MEK/ERK Signaling Contributes to the Maintenance of Human Embryonic Stem Cell Self-Renewal. Differentiation, 75, 299-307.
[81] Li, W., Wei, W., Zhu, S., Zhu, J., Shi, Y., Lin, T., Hao, E., Hayek, A., Deng, H. and Ding, S. (2009) Generation of Rat and Human Induced Pluripotent Stem Cells by Combining Genetic Reprogramming and Chemical Inhibitors. Cell Stem Cell, 4, 16-19.
[82] Marson, A., Foreman, R., Chevalier, B., Bilodeau, S., Kahn, M., Young, R.A. and Jaenisch, R. (2008) Wnt Signaling Promotes Reprogramming of Somatic Cells to Pluripotency. Cell Stem Cell, 3, 132-135.
[83] Rodriguez, A., Allegrucci, C. and Alberio, R. (2012) Modulation of Pluripotency in the Porcine Embryo and iPS Cells. PLoS ONE, 7, e49079.
[84] Yoshida, Y., Takahashi, K., Okita, K., Ichisaka, T. and Yamanaka, S. (2009) Hypoxia Enhances the Generation of Induced Pluripotent Stem Cells. Cell Stem Cell, 5, 237-241.
[85] Huangfu, D., Maehr, R., Guo, W., Eijkelenboom, A., Snitow, M., Chen, A.E. and Melton, D.A. (2008) Induction of Pluripotent Stem Cells by Defined Factors Is Greatly Improved by Small-Molecule Compounds. Nature Biotechnology, 26, 795-797.
[86] Li, W., Zhou, H., Abujarour, R., Zhu, S., Joo Young, J., Lin, T., Hao, E., Scholer, H.R., Hayek, A. and Ding, S. (2009) Generation of Human-Induced Pluripotent Stem Cells in the Absence of Exogenous Sox2. Stem Cells, 27, 2992-3000.
[87] Mikkelsen, T.S., Hanna, J., Zhang, X., Ku, M., Wernig, M., Schorderet, P., Bernstein, B.E., Jaenisch, R., Lander, E.S. and Meissner, A. (2008) Dissecting Direct Reprogramming through Integrative Genomic Analysis. Nature, 454, 49-55.
[88] Mali, P., Chou, B.K., Yen, J., Ye, Z., Zou, J., Dowey, S., Brodsky, R.A., Ohm, J.E., Yu, W., Baylin, S.B., Yusa, K., Bradley, A., Meyers, D.J., Mukherjee, C., Cole, P.A. and Cheng, L. (2010) Butyrate Greatly Enhances Derivation of Human Induced Pluripotent Stem Cells by Promoting Epigenetic Remodeling and the Expression of Pluripotency-Associated Genes. Stem Cells, 28, 713-720.
[89] Liang, G., Taranova, O., Xia, K. and Zhang, Y. (2010) Butyrate Promotes Induced Pluripotent Stem Cell Generation. The Journal of Biological Chemistry, 285, 25516-25521.
[90] Lee, Y.L., Peng, Q., Fong, S.W., Chen, A.C., Lee, K.F., Ng, E.H., Nagy, A. and Yeung, W.S. (2012) Sirtuin 1 Facilitates Generation of Induced Pluripotent Stem Cells from Mouse Embryonic Fibroblasts through the miR-34a and p53 Pathways. PLoS ONE, 7, e45633.
[91] Lee, J., Xia, Y., Son, M.Y., Jin, G., Seol, B., Kim, M.J., Son, M.J., Do, M., Lee, M., Kim, D., Lee, K. and Cho, Y.S. (2012) A Novel Small Molecule Facilitates the Reprogramming of Human Somatic Cells into a Pluripotent State and Supports the Maintenance of an Undifferentiated State of Human Pluripotent Stem Cells. Angewandte Chemie International Edition, 51, 12509-12513.
[92] Zhao, J., Hao, Y., Ross, J.W., Spate, L.D., Walters, E.M., Samuel, M.S., Rieke, A., Murphy, C.N. and Prather, R.S. (2010) Histone Deacetylase Inhibitors Improve in Vitro and in Vivo Developmental Competence of Somatic Cell Nuclear Transfer Porcine Embryos. Cellular Reprogramming, 12, 75-83.
[93] Kim, C., Amano, T., Park, J., Carter, M.G., Tian, X. and Yang, X. (2009) Improvement of Embryonic Stem Cell Line Derivation Efficiency with Novel Medium, Glucose Concentration, and Epigenetic Modifications. Cloning and Stem Cells, 11, 89-100.
[94] Lim, M.L., Vassiliev, I., Richings, N.M., Firsova, A.B., Zhang, C. and Verma, P.J. (2011) A novel, Efficient Method to Derive Bovine and Mouse Embryonic Stem Cells with in Vivo Differentiation Potential by Treatment with 5-Azacytidine. Theriogenology, 76, 133-142.
[95] Lee, R.C., Feinbaum, R.L. and Ambros, V. (1993) The C. elegans Heterochronic Gene lin-4 Encodes Small RNAs with Antisense Complementarity to lin-14. Cell, 75, 843-854.
[96] Wang, Y., Medvid, R., Melton, C., Jaenisch, R. and Blelloch, R. (2007) DGCR8 Is Essential for microRNA Biogenesis and Silencing of Embryonic Stem Cell Self-Renewal. Nature Genetics, 39, 380-385.
[97] Kanellopoulou, C., Muljo, S.A., Kung, A.L., Ganesan, S., Drapkin, R., Jenuwein, T., Livingston, D.M. and Rajewsky, K. (2005) Dicer-Deficient Mouse Embryonic Stem Cells Are Defective in Differentiation and Centromeric Silencing. Genes Development, 19, 489-501.
[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.
[99] Card, D.A., Hebbar, P.B., Li, L., Trotter, K.W., Komatsu, Y., Mishina, Y. and Archer, T.K. (2008) Oct4/Sox2-Regulated miR-302 Targets Cyclin D1 in Human Embryonic Stem Cells. Molecular and Cellular Biology, 28, 6426-6438.
[100] Anokye-Danso, F., Trivedi, C.M., Juhr, D., Gupta, M., Cui, Z., Tian, Y., Zhang, Y., Yang, W., Gruber, P.J., Epstein, J.A. and Morrisey, E.E. (2011) Highly Efficient miRNA-Mediated Reprogramming of Mouse and Human Somatic Cells to Pluripotency. Cell Stem Cell, 8, 376-388.
[101] Zhou, L., Wang, W., Liu, Y., Fernandez de Castro, J., Ezashi, T., Telugu, B.P.V.L., Roberts, R.M., Kaplan, H.J. and Dean, D.C. (2011) Differentiation of Induced Pluripotent Stem Cells of Swine into Rod Photoreceptors and Their Integration into the Retina. Stem Cells, 29, 972-980.
[102] Nelson, T.J., Martinez-Fernandez, A., Yamada, S., Perez-Terzic, C., Ikeda, Y. and Terzic, A. (2009) Repair of Acute Myocardial Infarction by Human Stemness Factors Induced Pluripotent Stem Cells. Circulation, 120, 408-416.
[103] Mauritz, C., Martens, A., Rojas, S.V., Schnick, T., Rathert, C., Schecker, N., Menke, S., Glage, S., Zweigerdt, R., Haverich, A., Martin, A. and Kutschka, I. (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. European Heart Journal, 32, 2634-2641.
[104] Pasha, Z., Haider, H.K. and Ashraf, M. (2011) Efficient Non-Viral Reprogramming of Myoblasts to Stemness with a Single Small Molecule to Generate Cardiac Progenitor Cells. PLoS ONE, 6, e23667.
[105] Singla, D.K., Long, X., Glass, C., Singla, R.D. and Yan, B. (2011) Induced Pluripotent Stem (iPS) Cells Repair and Regenerate Infarcted Myocardium. Molecular Pharmaceutics, 8, 1573-1581.
[106] Ahmed, R.P., 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.
[107] Templin, C., Zweigerdt, R., Schwanke, K., Olmer, R., Ghadri, J.R., Emmert, M.Y., Muller, E., Kuest, S.M., Cohrs, S., Schibli, R., Kronen, P., Hilbe, M., Reinisch, A., Strunk, D., Haverich, A., Hoerstrup, S., Luscher, T.F., Kaufmann, P.A., Landmesser, U. and Martin, U. (2012) Transplantation and Tracking of Human-Induced Pluripotent Stem Cells in a Pig Model of Myocardial Infarction: Assessment of Cell Survival, Engraftment, and Distribution by Hybrid Single Photon Emission Computed Tomography/Computed Tomography of Sodium Iodide Symporter Transgene Expression. Circulation, 126, 430-439.
[108] Li, X., Zhang, F., Song, G., Gu, W., Chen, M., Yang, B., Li, D., Wang, D. and Cao, K. (2013) Intramyocardial Injection of Pig Pluripotent Stem Cells Improves Left Ventricular Function and Perfusion: A Study in a Porcine Model of Acute Myocardial Infarction. PLoS ONE, 8, e66688.
[109] Park, J., Kim, C., Tang, Y., Amano, T., Lin, C.J. and Tian, X.C. (2011) Reprogramming of Mouse Fibroblasts to an Intermediate State of Differentiation by Chemical Induction. Cellular Reprogramming, 13, 121-131.
[110] Esteban, M.A., Wang, T., Qin, B., Yang, J., Qin, D., Cai, J., Li, W., Weng, Z., Chen, J., Ni, S., Chen, K., Li, Y., Liu, K., Xu, J., Zhang, S., Li, F., He, W., Labuda, K., Song, Y., Peterbauer, Y., Wolbank, S., Redl, H., Zhong, M., Cai, D., Zeng, L. and Pei, D. (2010) Vitamin C Enhances the Generation of Mouse and Human Induced Pluripotent Stem Cells. Cell Stem Cell, 6, 71-79.
[111] Kawamura, T., Suzuki, J., Wang, Y., Menendez, S., Morera, L., Raya, A., Wahl, G.M. and Izpisúa Belmonte, J.C. (2009) Linking the p53 Tumour Suppressor Pathway to Somatic Cell Reprogramming. Nature, 460, 1140-1144.
[112] Strom, E., Sathe, S., Komarov, P.G., Chernova, O.B., Pavlovska, I., Shyshynova, I., Bosykh, D., Burdelya, L.G., Macklis, R.M., Sdaliter, R., Komarova, E.A. and Gudkov, A.V. (2006) Small-Molecule Inhibitor of p53 Binding to Mitochondria Protects Mice from Gamma Radiation. Nature Chemical Biology, 2, 474-479.
[113] Chen, S., Do, J.T., Zhang, Q., Yao, S., Yan, F., Peters, E.C., Scholer, H.R., Schultz, P.G. and Ding, S. (2006) Self-Renewal of Embryonic Stem Cells by a Small Molecule. Proceedings of the National Academy of Sciences of the United States of America, 103, 17266-17271.
[114] 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., Akutsu, H., Liu, D.R., Rubin, L.L. and Eggan, K. (2009) A Small-Molecule Inhibitor of Tgf-Beta Signaling Replaces Sox2 in Reprogramming by Inducing Nanog. Cell Stem Cell, 5, 491-503.

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