Cellular models for disease exploring and drug screening

Zhi-kun Li1,2, Qi Zhou1()

PDF(137 KB)
PDF(137 KB)
Protein Cell ›› 2010, Vol. 1 ›› Issue (4) : 355-362. DOI: 10.1007/s13238-010-0027-9
REVIEW
REVIEW

Cellular models for disease exploring and drug screening

  • Zhi-kun Li1,2, Qi Zhou1()
Author information +
History +

Abstract

The biopharmaceutical industry has been greatly promoted by the application of drug and disease models, including both animal and cellular models. In particular, the emergence of induced pluripotent stem cells (iPSC) makes it possible to create a large number of disease-specific cells in vitro. This review introduces the most widely applied models and their specialties.

Keywords

cellular models / disease models / induced pluripotential stem cells / neural diseases

Cite this article

Download citation ▾
Zhi-kun Li, Qi Zhou. Cellular models for disease exploring and drug screening. Prot Cell, 2010, 1(4): 355‒362 https://doi.org/10.1007/s13238-010-0027-9

References

[1] Acharya, M.M., Christie, L.A., Lan, M.L., Donovan, P.J., Cotman, C.W., Fike, J.R., and Limoli, C.L. (2009). Rescue of radiation-induced cognitive impairment through cranial transplantation of human embryonic stem cells. Proc Natl Acad Sci U S A 106, 19150–19155 .10.1073/pnas.0909293106
[2] Bain, G., Kitchens, D., Yao, M., Huettner, J.E., and Gottlieb, D.I. (1995). Embryonic stem cells express neuronal properties in vitro. Dev Biol 168, 342–357 .10.1006/dbio.1995.1085
[3] Bao, S., Tang, F., Li, X., Hayashi, K., Gillich, A., Lao, K., and Surani, M.A. (2009). Epigenetic reversion of post-implantation epiblast to pluripotent embryonic stem cells. Nature 461, 1292–1295 .10.1038/nature08534
[4] Ben-Nun, I.F., and Benvenisty, N. (2006). Human embryonic stem cells as a cellular model for human disorders. Mol Cell Endocrinol 252, 154–159 .10.1016/j.mce.2006.03.034
[5] Brons, I.G., Smithers, L.E., Trotter, M.W., Rugg-Gunn, P., Sun, B., Chuva de Sousa Lopes, S.M., Howlett, S.K., Clarkson, A., Ahrlund-Richter, L., Pedersen, R.A., . (2007). Derivation of pluripotent epiblast stem cells from mammalian embryos. Nature 448, 191–195 .10.1038/nature05950
[6] Brown, J.P., Wei, W., and Sedivy, J.M. (1997). Bypass of senescence after disruption of p21CIP1/WAF1 gene in normal diploid human fibroblasts. Science 277, 831–834 .10.1126/science.277.5327.831
[7] Buchheiser, A., Liedtke, S., Looijenga, L.H., and Kogler, G. (2009). Cord blood for tissue regeneration. J Cell Biochem 108, 762–768 .10.1002/jcb.22320
[8] Bunz, F., Dutriaux, A., Lengauer, C., Waldman, T., Zhou, S., Brown, J.P., Sedivy, J.M., Kinzler, K.W., and Vogelstein, B. (1998). Requirement for p53 and p21 to sustain G2 arrest after DNA damage. Science 282, 1497–1501 .10.1126/science.282.5393.1497
[9] Buzanska, L., Sypecka, J., Molteni, S.N., Compagnoni, A., Hogberg, H.T., Del Torchio, R., Domanska-Janik, K., Zimmer, J., and Coecke, S. (2009). A human stem cell based model for identifying adverse effects of organic and inorganic chemicals on the developing nervous system. Stem Cells 27, 2591–2601 .10.1002/stem.179
[10] Cartwright, E.J. (2009). Large-scale mouse mutagenesis. Methods Mol Biol 561, 275–283 .10.1007/978-1-60327-019-9_18
[11] Chamberlain, S.J., Li, X.J., and Lalande, M. (2008). Induced pluripotent stem (iPS) cells as in vitro models of human neurogenetic disorders. Neurogenetics 9, 227–235 .10.1007/s10048-008-0147-z
[12] Chan, E.M., Ratanasirintrawoot, S., Park, I.H., Manos, P.D., Loh, Y.H., Huo, H., Miller, J.D., Hartung, O., Rho, J., Ince, T.A., . (2009). Live cell imaging distinguishes bona fide human iPS cells from partially reprogrammed cells. Nat Biotechnol 27, 1033–1037 .10.1038/nbt.1580
[13] Chin, M.H., Mason, M.J., Xie, W., Volinia, S., Singer, M., Peterson, C., Ambartsumyan, G., Aimiuwu, O., Richter, L., Zhang, J., . (2009). Induced pluripotent stem cells and embryonic stem cells are distinguished by gene expression signatures. Cell Stem Cell 5, 111–123 .10.1016/j.stem.2009.06.008
[14] Cross, D.M., and Bayliss, M.K. (2000). A commentary on the use of hepatocytes in drug metabolism studies during drug discovery and development. Drug Metab Rev 32, 219–240 .10.1081/DMR-100100574
[15] Dan, Y.Y., and Yeoh, G.C. (2008). Liver stem cells: A scientific and clinical perspective. J Gastroenterol Hepatol 23, 687–698 .10.1111/j.1440-1746.2008.05383.x
[16] Darimont, C. (2003). Immortalization of human preadipocytes. Biochimie 85, 1231–1233 .10.1016/j.biochi.2003.10.015
[17] Dimos, J.T., Rodolfa, K.T., Niakan, K.K., Weisenthal, L.M., Mitsumoto, H., Chung, W., Croft, G.F., Saphier, G., Leibel, R., Goland, R., . (2008). Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science 321, 1218–1221 .10.1126/science.1158799
[18] Dixon, S.J., and Stockwell, B.R. (2009). Identifying druggable disease-modifying gene products. Curr Opin Chem Biol 13, 549–555 .10.1016/j.cbpa.2009.08.003
[19] Ebert, A.D., Yu, J., Rose, F.F., Jr., Mattis, V.B., Lorson, C.L., Thomson, J.A., and Svendsen, C.N. (2009). Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature 457, 277–280 .10.1038/nature07677
[20] Feher, M., and Schmidt, J.M. (2003). Property distributions: differences between drugs, natural products, and molecules from combinatorial chemistry. J Chem Inf Comput Sci 43, 218–227 .10.1021/ci0200467
[21] Hajkova, P. (2007). Genetic and epigenetic regulators of pluripotency. Cell 128, 747–762 10.1016/j.cell.2007.02.010
[22] Hajkova, P., Ancelin, K., Waldmann, T., Lacoste, N., Lange, U.C., Cesari, F., Lee, C., Almouzni, G., Schneider, R., and Surani, M.A. (2008). Chromatin dynamics during epigenetic reprogramming in the mouse germ line. Nature 452, 877–881 .10.1038/nature06714
[23] Hajkova, P., Erhardt, S., Lane, N., Haaf, T., El-Maarri, O., Reik, W., Walter, J., and Surani, M.A. (2002). Epigenetic reprogramming in mouse primordial germ cells. Mech Dev 117, 15–23 .10.1016/S0925-4773(02)00181-8
[24] Hanna, J., Saha, K., Pando, B., van Zon, J., Lengner, C.J., Creyghton, M.P., van Oudenaarden, A., and Jaenisch, R. (2009). Direct cell reprogramming is a stochastic process amenable to acceleration. Nature 462, 595–601 .10.1038/nature08592
[25] Huang, J.Y., Chen, T.T., Liu, X.S., Jiang, J., Li, J.S., Li, D.S., Liu, X.S., Li, W., Kang, J.H., and Pei, G. (2009). More synergetic cooperation of Yamanaka factors in induced pluripotent stem cells than in embryonic stem cells. Cell Res 19, 1127–1138 .10.1038/cr.2009.106
[26] Hyun, I., Taylor, P., Testa, G., Dickens, B., Jung, K.W., McNab, A., Robertson, J., Skene, L., and Zoloth, L. (2007). Ethical standards for human-to-animal chimera experiments in stem cell research. Cell Stem Cell 1, 159–163 .10.1016/j.stem.2007.07.015
[27] Insoo Hyun, K.H., Rudolf Jaenisch, and Shinya Yamanaka (2007). New advances in iPS cell research do not obviate the need for human embryonic stem cells. Cell Stem Cell 11, 367–368 .10.1016/j.stem.2007.09.006
[28] Jakel, R.J., Schneider, B.L., and Svendsen, C.N. (2004). Using human neural stem cells to model neurological disease. Nature Rev Genet 5, 136–144 .10.1038/nrg1268
[29] Jensen, J., Hyllner, J., and Bjorquist, P. (2009). Human embryonic stem cell technologies and drug discovery. J Cell Physiol 219, 513–519 .10.1002/jcp.21732
[30] Kawasaki, H., Mizuseki, K., Nishikawa, S., Kaneko, S., Kuwana, Y., Nakanishi, S., Nishikawa, S.I., and Sasai, Y. (2000). Induction of midbrain dopaminergic neurons from ES cells by stromal cell-derived inducing activity. Neuron 28, 31–40 .10.1016/S0896-6273(00)00083-0
[31] Koch, P., Kokaia, Z., Lindvall, O., and Brustle, O. (2009). Emerging concepts in neural stem cell research: autologous repair and cell-based disease modelling. Lancet Neurol 8, 819–829 .10.1016/S1474-4422(09)70202-9
[32] Kola, I., and Landis, J. (2004). Can the pharmaceutical industry reduce attrition rates? Nat Rev Drug Discov 3, 711–715 .10.1038/nrd1470
[33] Lee, G., Papapetrou, E.P., Kim, H., Chambers, S.M., Tomishima, M.J., Fasano, C.A., Ganat, Y.M., Menon, J., Shimizu, F., Viale, A., . (2009). Modelling pathogenesis and treatment of familial dysautonomia using patient-specific iPSCs. Nature 461, 402–406 .10.1038/nature08320
[34] Maehr, R., Chen, S., Snitow, M., Ludwig, T., Yagasaki, L., Goland, R., Leibel, R.L., and Melton, D.A. (2009). Generation of pluripotent stem cells from patients with type 1 diabetes. Proc Natl Acad Sci U S A 106, 15768–15773 .10.1073/pnas.0906894106
[35] Matsui, Y., Zsebo, K., and Hogan, B.L. (1992). Derivation of pluripotential embryonic stem cells from murine primordial germ cells in culture. Cell 70, 841–847 .10.1016/0092-8674(92)90317-6
[36] Muotri, A.R., Nakashima, K., Toni, N., Sandler, V.M., and Gage, F.H. (2005). Development of functional human embryonic stem cell-derived neurons in mouse brain. Proc Natl Acad Sci U S A 102, 18644–18648 .10.1073/pnas.0509315102
[37] Nakagawa, M., Koyanagi, M., Tanabe, K., Takahashi, K., Ichisaka, T., Aoi, T., Okita, K., Mochiduki, Y., Takizawa, N., and Yamanaka, S. (2008). Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol 26, 101–106 .10.1038/nbt1374
[38] Newman, D.J., and Cragg, G.M. (2007). Natural products as sources of new drugs over the last 25 years. J Nat Prod 70, 461–477 .10.1021/np068054v
[39] Norstrom, A., Akesson, K., Hardarson, T., Hamberger, L., Bjorquist, P., and Sartipy, P. (2006). Molecular and pharmacological properties of human embryonic stem cell-derived cardiomyocytes. Exp Biol Med 231, 1753–1762 .
[40] Obinata, M. (2007). The immortalized cell lines with differentiation potentials: their establishment and possible application. Cancer Sci 98, 275–283 .10.1111/j.1349-7006.2007.00399.x
[41] Okita, K., Nakagawa, M., Hong, H.J., Ichisaka, T., and Yamanaka, S. (2008). Generation of mouse induced pluripotent stem cells without viral vectors. Science 322, 949–953 .10.1126/science.1164270
[42] Pang, Y.Q., Li, W.X., Ma, R.L., Ji, W.D., Wang, Q., Li, D.C., Xiao, Y.M., Wei, Q., Lai, Y.D., Yang, P., . (2008). Development of human cell models for assessing the carcinogenic potential of chemicals. Toxicol Appl Pharmacol 232, 478–486 .10.1016/j.taap.2008.08.009
[43] Park, I.H., Arora, N., Huo, H., Maherali, N., Ahfeldt, T., Shimamura, A., Lensch, M.W., Cowan, C., Hochedlinger, K., and Daley, G.Q. (2008). Disease-specific induced pluripotent stem cells. Cell 134, 877–886 .10.1016/j.cell.2008.07.041
[44] Patel, E., Wang, B., Lien, L.L., Wang, Y.C., Yang, L.J., Moreb, J.S., and Chang, L.J. (2009). Diverse T-cell differentiation potentials of human fetal thymus, fetal liver, cord blood and adult bone marrow CD34 cells on lentiviral Delta-like-1-modified mouse stromal cells. Immunology 128, e497–505 .10.1111/j.1365-2567.2008.03013.x
[45] Raya, A., Rodriguez-Piza, I., Guenechea, G., Vassena, R., Navarro, S., Barrero, M.J., Consiglio, A., Castella, M., Rio, P., Sleep, E., . (2009). Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells. Nature 460, 53–59 .10.1038/nature08129
[46] Rohwedel, J., Guan, K., Hegert, C., and Wobus, A.M. (2001). Embryonic stem cells as an in vitro model for mutagenicity, cytotoxicity and embryotoxicity studies: present state and future prospects. Toxicol In Vitro 15, 741–753 .10.1016/S0887-2333(01)00074-1
[47] Sartipy, P., Bjorquist, P., Strehl, R., and Hyllner, J. (2007). The application of human embryonic stem cell technologies to drug discovery. Drug Discov Today 12, 688–699 .10.1016/j.drudis.2007.07.005
[48] Schneider, B.L., Seehus, C.R., Capowski, E.E., Aebischer, P., Zhang, C., and Svendsen, C.N. (2007). Over-expression of alpha-synuclein in human neural progenitors leads to specific changes in fate and differentiation. Hum Mol Genet 16, 651–666 .10.1093/hmg/ddm008
[49] 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 .10.1016/j.cell.2009.07.039
[50] Simon, L., Ekman, G.C., Kostereva, N., Zhang, Z., Hess, R.A., Hofmann, M.C., and Cooke, P.S. (2009). Direct transdifferentiation of stem/progenitor spermatogonia into reproductive and nonreproductive tissues of all germ layers. Stem Cells 27, 1666–1675 .10.1002/stem.93
[51] Smith, A. (2009). Nanog Is the Gateway to the Pluripotent Ground State. Cell 138, 722–723 .10.1016/j.cell.2009.07.039
[52] Soldner, F., Hockemeyer, D., Beard, C., Gao, Q., Bell, G.W., Cook, E.G., Hargus, G., Blak, A., Cooper, O., Mitalipova, M., . (2009). Parkinson's disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell 136, 964–977 .10.1016/j.cell.2009.02.013
[53] Soucy, T.A., Smith, P.G., Milhollen, M.A., Berger, A.J., Gavin, J.M., Adhikari, S., Brownell, J.E., Burke, K.E., Cardin, D.P., Critchley, S., . (2009). An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature 458, 732–736 .10.1038/nature07884
[54] Sridharan, R., Tchieu, J., Mason, M.J., Yachechko, R., Kuoy, E., Horvath, S., Zhou, Q., and Plath, K. (2009). Role of the murine reprogramming factors in the induction of pluripotency. Cell 136, 364–377 .10.1016/j.cell.2009.01.001
[55] Stadtfeld, M., Nagaya, M., Utikal, J., Weir, G., and Hochedlinger, K. (2008). Induced pluripotent stem cells generated without viral integration. Science 322, 945–949 .10.1126/science.1162494
[56] Stout, J.T., and Caskey, C.T. (1988). The Lesch-Nyhan syndrome: clinical, molecular and genetic-aspects. Trends Genet 4, 175–178 .10.1016/0168-9525(88)90024-8
[57] Sundstrom, L., Morrison, B., Bradley, M., and Pringle, A. (2005). Organotypic cultures as tools for functional screening in the CNS. Drug Discov Today 10, 993–1000 .10.1016/S1359-6446(05)03502-6
[58] Surani, M.A., Durcova-Hills, G., Hajkova, P., Hayashi, K., and Tee, W.W. (2008). Germ line, stem cells, and epigenetic reprogramming. Cold Spring Harb Symp Quant Biol 73, 9–15 .
[59] Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., and Yamanaka, S. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861–872 .10.1016/j.cell.2007.11.019
[60] 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 .10.1016/j.cell.2006.07.024
[61] Tanaka, T., Tohyama, S., Murata, M., Nomura, F., Kaneko, T., Chen, H., Hattori, F., Egashira, T., Seki, T., Ohno, Y., . (2009). In vitro pharmacologic testing using human induced pluripotent stem cell-derived cardiomyocytes. Biochem Biophys Res Commun 385, 497–502 .10.1016/j.bbrc.2009.05.073
[62] Tanaka, T., Tohyama, S., Murata, M., Nomura, F., Kaneko, T., Chen, H., Hattori, F., Egashira, T., Seki, T., Ohno, Y., Koshimizu, U., Yuasa, S., Ogawa, S., Yamanaka, S., Yasuda, K., and Fukuda, K. (2009). In vitro pharmacologic testing using human induced pluripotent stem cell-derived cardiomyocytes. Biochem Biophys Res Commun 385, 497–502 .10.1016/j.bbrc.2009.05.073
[63] Tesar, P.J., Chenoweth, J.G., Brook, F.A., Davies, T.J., Evans, E.P., Mack, D.L., Gardner, R.L., and McKay, R.D. (2007). New cell lines from mouse epiblast share defining features with human embryonic stem cells. Nature 448, 196–199 .10.1038/nature05972
[64] Theoharides, T.C., Kempuraj, D., Tagen, M., Vasiadi, M., and Cetrulo, C.L. (2006). Human umbilical cord blood-derived mast cells—A unique model for the study of neuro-immuno-endocrine interactions. Stem Cell Rev 2, 143–153 .10.1385/SCR:2:2:143
[65] 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 .10.1126/science.282.5391.1145
[66] Utikal, J., Polo, J.M., Stadtfeld, M., Maherali, N., Kulalert, W., Walsh, R.M., Khalil, A., Rheinwald, J.G., and Hochedlinger, K. (2009). Immortalization eliminates a roadblock during cellular reprogramming into iPS cells. Nature 460, 1145–1148 .10.1038/nature08285
[67] Vallier, L., Touboul, T., Chng, Z., Brimpari, M., Hannan, N., Millan, E., Smithers, L.E., Trotter, M., Rugg-Gunn, P., Weber, A., . (2009). Early cell fate decisions of human embryonic stem cells and mouse epiblast stem cells are controlled by the same signalling pathways. PLos One 4, e6082.10.1371/journal.pone.0006082
[68] van de Ven, C., Collins, D., Bradley, M.B., Morris, E., and Cairo, M.S. (2007). The potential of umbilical cord blood multipotent stem cells for nonhematopoietic tissue and cell regeneration. Exp Hematol 35, 1753–1765 .10.1016/j.exphem.2007.08.017
[69] Vassilev, L.T., Vu, B.T., Graves, B., Carvajal, D., Podlaski, F., Filipovic, Z., Kong, N., Kammlott, U., Lukacs, C., Klein, C., . (2004). In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 303, 844–848 .10.1126/science.1092472
[70] Waterston, R.H., Lindblad-Toh, K., Birney, E., Rogers, J., Abril, J.F., Agarwal, P., Agarwala, R., Ainscough, R., Alexandersson, M., An, P., . (2002). Initial sequencing and comparative analysis of the mouse genome. Nature 420, 520–562 .10.1038/nature01262
[71] Wright, L.S., Prowse, K.R., Wallace, K., Linskens, M.H.K., and Svendsen, C.N. (2006). Human progenitor cells isolated from the developing cortex undergo decreased neurogenesis and eventual senescence following expansion in vitro. Exp Cell Res 312, 2107–2120 .10.1016/j.yexcr.2006.03.012
[72] Yamada, T., Yoshikawa, M., Kanda, S., Kato, Y., Nakajima, Y., Ishizaka, S., and Tsunoda, Y. (2002). In vitro differentiation of embryonic stem cells into hepatocyte-like cells identified by cellular uptake of indocyanine green. Stem Cells 20, 146–154 .10.1634/stemcells.20-2-146
[73] Ying, Q.L., Nichols, J., Chambers, I., and Smith, A. (2003). BMP induction of Id proteins suppresses differentiation and sustains embryonic stem cell self-renewal in collaboration with STAT3. Cell 115, 281–292 .10.1016/S0092-8674(03)00847-X
[74] Ying, Q.L., Wray, J., Nichols, J., Batlle-Morera, L., Doble, B., Woodgett, J., Cohen, P., and Smith, A. (2008). The ground state of embryonic stem cell self-renewal. Nature 453, 519–523 .10.1038/nature06968
[75] Yu, J., Hu, K., Smuga-Otto, K., Tian, S., Stewart, R., Slukvin, II, and Thomson, J.A. (2009). Human induced pluripotent stem cells free of vector and transgene sequences. Science 324, 797–801 .10.1126/science.1172482
[76] Yu, J.Y., Vodyanik, M.A., Smuga-Otto, K., Antosiewicz-Bourget, J., Frane, J.L., Tian, S., Nie, J., Jonsdottir, G.A., Ruotti, V., Stewart, R., . (2007). Induced pluripotent stem cell lines derived from human somatic cells. Science 318, 1917–1920 .10.1126/science.1151526
[77] Zeh, K., Sanders, P., Londo, P., Crute, J.J., Pollok, B.A., and Whitney, M.A. (2003). Gain-of-function somatic cell lines for drug discovery applications generated by homologous recombination. Assay Drug Dev Technol 1, 755–765 .10.1089/154065803772613390
[78] Zhang, S.C., Wernig, M., Duncan, I.D., Brustle, O., and Thomson, J.A. (2001). In vitro differentiation of transplantable neural precursors from human embryonic stem cells. Nature Biotechnology 19, 1129–1133 .10.1038/nbt1201-1129
[79] Zhao, X.Y., Li, W., Lv, Z., Liu, L., Tong, M., Hai, T., Hao, J., Guo, C.L., Ma, Q.W., Wang, L., . (2009). iPS cells produce viable mice through tetraploid complementation. Nature 461, 86–90 .10.1038/nature08267
[80] Zhou, H.Y., Wu, S.L., Joo, J.Y., Zhu, S.Y., Han, D.W., Lin, T.X., Trauger, S., Bien, G., Yao, S., Zhu, Y., . (2009). Generation of Induced Pluripotent Stem Cells Using Recombinant Proteins. Cell Stem Cell 4, 381–384 .10.1016/j.stem.2009.04.005
AI Summary AI Mindmap
PDF(137 KB)

Accesses

Citations

Detail

Sections
Recommended

/