摘要
背景:随着研究的深入,诱导多能干细胞被应用于疾病模型建立、药物筛选和再生医学等多个研究领域,尤其是应用于神经系统疾病的研究。目的:总结诱导多能干细胞目前的进展并结合相关领域的最新研究提出问题和展望。方法:第一作者检索2006年1月至2014年9月Pub Med数据库中有关诱导多能干细胞的相关文献,检索词为"i PS,induced pluripotent stem cell",包括综述、临床研究和基础研究,最终纳入60篇文献。结果与结论:2006年Yamanaka团队的诱导多能干细胞问世至2012年诺贝尔奖的颁发,短短6年间诱导多能干细胞相关的研究不断取得突破。诱导多能干细胞研究在疾病模型、药物筛选和再生医学等方面拥有广阔的前景,目前存在包括重编程方式、细胞稳定性、临床转化等一系列问题亟待解决,仍需进一步研究深化。
BACKGROUND: With the development of the research, induced pluripotent stem cells are applied to the build of disease model, drug screening, regenerative medicine, and many other research fields, and have made significant achievements, especially in the study of nervous system diseases. OBJECTIVE: To summarize the recent development of induced pluripotent stem cells and to raise problems and prospects based on the latest research in this field. METHODS: The first author searched the Pub Med database for articles about the induced pluripotent stem cells, including reviews, clinical research and basic research, published from January 2006 to September 2014. The keywords were "i PS, induced pluripotent stem cell", and finally 60 articles were included in result analysis. RESULTS AND CONCLUSION: Induced pluripotent stem cell research continues to make breakthrough from its discovery by Yamanaka's team in 2006 to winning Nobel Prize in 2012. Induced pluripotent stem cell research has broad prospects in the disease model construction, drug screening and regenerative medicine. Currently, problems such as reprogramming methods, cell stability, and clinical transformation still need to be solved, and further researches are necessary.
引文
[1]Somorjai IM,Lohmann JU,Holstein TW,et al.Stem cells:a view from the roots.Biotechnol J.2012;7(6):704-722.
[2]Takahashi K,Yamanaka S.Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.Cell.2006;126(4):663-676.
[3]Aoi T,Yae K,Nakagawa M,et al.Generation of pluripotent stem cells from adult mouse liver and stomach cells.Science.2008;321(5889):699-702.
[4]Hanna J,Markoulaki S,Schorderet P,et al.Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency.Cell.2008;133(2):250-264.
[5]Kim JB,Zaehres H,Wu G,et al.Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors.Nature.2008;454(7204):646-650.
[6]Takahashi K,Tanabe K,Ohnuki M,et al.Induction of pluripotent stem cells from adult human fibroblasts by defined factors.Cell.2007;131(5):861-872.
[7]Yu J,Vodyanik MA,Smuga-Otto K,et al.Induced pluripotent stem cell lines derived from human somatic cells.Science.2007;318(5858):1917-1920.
[8]Grskovic M,Javaherian A,Strulovici B,et al.Induced pluripotent stem cells--opportunities for disease modelling and drug discovery.Nat Rev Drug Discov.2011;10(12):915-929.
[9]Devine MJ,Ryten M,Vodicka P,et al.Parkinson's disease induced pluripotent stem cells with triplication of theα-synuclein locus.Nat Commun.2011;2:440.
[10]Israel MA,Yuan SH,Bardy C,et al.Probing sporadic and familial Alzheimer's disease using induced pluripotent stem cells.Nature.2012;482(7384):216-220.
[11]Yagi T,Ito D,Okada Y,et al.Modeling familial Alzheimer's disease with induced pluripotent stem cells.Hum Mol Genet.2011;20(23):4530-4539.
[12]Yahata N,Asai M,Kitaoka S,et al.Anti-Aβdrug screening platform using human i PS cell-derived neurons for the treatment of Alzheimer's disease.PLo S One.2011;6(9):e25788.
[13]Brennand KJ,Simone A,Jou J,et al.Modelling schizophrenia using human induced pluripotent stem cells.Nature.2011;473(7346):221-225.
[14]Yamanaka S.Elite and stochastic models for induced pluripotent stem cell generation.Nature.2009;460(7251):49-52.
[15]Ebert AD,Svendsen CN.Human stem cells and drug screening:opportunities and challenges.Nat Rev Drug Discov.2010;9(5):367-372.
[16]Seibler P,Graziotto J,Jeong H,et al.Mitochondrial Parkin recruitment is impaired in neurons derived from mutant PINK1induced pluripotent stem cells.J Neurosci.2011;31(16):5970-5976.
[17]Ding Q,Lee YK,Schaefer EA,et al.A TALEN genome-editing system for generating human stem cell-based disease models.Cell Stem Cell.2013;12(2):238-251.
[18]Gaj T,Gersbach CA,Barbas CF 3rd.ZFN,TALEN,and CRISPR/Cas-based methods for genome engineering.Trends Biotechnol.2013;31(7):397-405.
[19]Hockemeyer D,Soldner F,Beard C,et al.Efficient targeting of expressed and silent genes in human ESCs and i PSCs using zinc-finger nucleases.Nat Biotechnol.2009;27(9):851-857.
[20]Horii T,Morita S,Kimura M,et al.Genome engineering of mammalian haploid embryonic stem cells using the Cas9/RNA system.Peer J.2013;1:e230.
[21]Chen H,Qian K,Du Z,et al.Modeling ALS with i PSCs reveals that mutant SOD1 misregulates neurofilament balance in motor neurons.Cell Stem Cell.2014;14(6):796-809.
[22]Espuny-Camacho I,Michelsen KA,Gall D,et al.Pyramidal neurons derived from human pluripotent stem cells integrate efficiently into mouse brain circuits in vivo.Neuron.2013;77(3):440-456.
[23]Shi Y,Kirwan P,Livesey FJ.Directed differentiation of human pluripotent stem cells to cerebral cortex neurons and neural networks.Nat Protoc.2012;7(10):1836-1846.
[24]Shi Y,Kirwan P,Smith J,et al.Human cerebral cortex development from pluripotent stem cells to functional excitatory synapses.Nat Neurosci.2012;15(3):477-486.
[25]Heinrich EM,Dimmeler S.Micro RNAs and stem cells:control of pluripotency,reprogramming,and lineage commitment.Circ Res.2012;110(7):1014-1022.
[26]Kretsovali A,Hadjimichael C,Charmpilas N.Histone deacetylase inhibitors in cell pluripotency,differentiation,and reprogramming.Stem Cells Int.2012;2012:184154.
[27]Esteban MA,Wang T,Qin B,et al.Vitamin C enhances the generation of mouse and human induced pluripotent stem cells.Cell Stem Cell.2010;6(1):71-79.
[28]Nakagawa M,Takizawa N,Narita M,et al.Promotion of direct reprogramming by transformation-deficient Myc.Proc Natl Acad Sci U S A.2010;107(32):14152-14157.
[29]Tong M,Lv Z,Liu L,et al.Mice generated from tetraploid complementation competent i PS cells show similar developmental features as those from ES cells but are prone to tumorigenesis.Cell Res.2011;21(11):1634-1637.
[30]Bayart E,Cohen-Haguenauer O.Technological overview of i PS induction from human adult somatic cells.Curr Gene Ther.2013;13(2):73-92.
[31]Okita K,Matsumura Y,Sato Y,et al.A more efficient method to generate integration-free human i PS cells.Nat Methods.2011;8(5):409-412.
[32]Yu P,Lu Y,Jordan BJ,et al.Nonviral minicircle generation of induced pluripotent stem cells compatible with production of chimeric chickens.Cell Reprogram.2014;16(5):366-378.
[33]Stadtfeld M,Nagaya M,Utikal J,et al.Induced pluripotent stem cells generated without viral integration.Science.2008;322(5903):945-949.
[34]Mandal PK,Rossi DJ.Reprogramming human fibroblasts to pluripotency using modified m RNA.Nat Protoc.2013;8(3):568-582.
[35]Yoshioka N,Gros E,Li HR,et al.Efficient generation of human i PSCs by a synthetic self-replicative RNA.Cell Stem Cell.2013;13(2):246-254.
[36]Kim D,Kim CH,Moon JI,et al.Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins.Cell Stem Cell.2009;4(6):472-476.
[37]González F,BouéS,Izpisúa Belmonte JC.Methods for making induced pluripotent stem cells:reprogrammingàla carte.Nat Rev Genet.2011;12(4):231-242.
[38]Hou P,Li Y,Zhang X,et al.Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds.Science.2013;341(6146):651-654.
[39]Zhao T,Zhang ZN,Rong Z,et al.Immunogenicity of induced pluripotent stem cells.Nature.2011;474(7350):212-215.
[40]Scheiner ZS,Talib S,Feigal EG.The potential for immunogenicity of autologous induced pluripotent stem cell-derived therapies.J Biol Chem.2014;289(8):4571-4577.
[41]Lu X,Zhao T.Clinical therapy using i PSCs:hopes and challenges.Genomics Proteomics Bioinformatics.2013;11(5):294-298.
[42]Laurent LC,Ulitsky I,Slavin I,et al.Dynamic changes in the copy number of pluripotency and cell proliferation genes in human ESCs and i PSCs during reprogramming and time in culture.Cell Stem Cell.2011;8(1):106-118.
[43]Mayshar Y,Ben-David U,Lavon N,et al.Identification and classification of chromosomal aberrations in human induced pluripotent stem cells.Cell Stem Cell.2010;7(4):521-531.
[44]Sareen D,Mc Millan E,Ebert AD,et al.Chromosome 7 and 19trisomy in cultured human neural progenitor cells.PLo S One.2009;4(10):e7630.
[45]Gore A,Li Z,Fung HL,et al.Somatic coding mutations in human induced pluripotent stem cells.Nature.2011;471(7336):63-67.
[46]Hussein SM,Batada NN,Vuoristo S,et al.Copy number variation and selection during reprogramming to pluripotency.Nature.2011;471(7336):58-62.
[47]Lister R,Pelizzola M,Kida YS,et al.Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells.Nature.2011;471(7336):68-73.
[48]Pasi CE,Dereli-z A,Negrini S,et al.Genomic instability in induced stem cells.Cell Death Differ.2011;18(5):745-753.
[49]Cheng L,Hansen NF,Zhao L,et al.Low incidence of DNA sequence variation in human induced pluripotent stem cells generated by nonintegrating plasmid expression.Cell Stem Cell.2012;10(3):337-344.
[50]Young MA,Larson DE,Sun CW,et al.Background mutations in parental cells account for most of the genetic heterogeneity of induced pluripotent stem cells.Cell Stem Cell.2012;10(5):570-582.
[51]Stadtfeld M,Hochedlinger K.Induced pluripotency:history,mechanisms,and applications.Genes Dev.2010;24(20):2239-2263.
[52]Hayden EC.California ponders cell-banking venture.Nature.2011;472(7344):403.
[53]Frey-Vasconcells J,Whittlesey KJ,Baum E,et al.Translation of stem cell research:points to consider in designing preclinical animal studies.Stem Cells Transl Med.2012;1(5):353-358.
[54]Philippens IH,'t Hart BA,Torres G.The MPTP marmoset model of parkinsonism:a multi-purpose non-human primate model for neurodegenerative diseases.Drug Discov Today.2010;15(23-24):985-990.
[55]Bihel E,Pro-Sistiaga P,Letourneur A,et al.Permanent or transient chronic ischemic stroke in the non-human primate:behavioral,neuroimaging,histological,and immunohistochemical investigations.J Cereb Blood Flow Metab.2010;30(2):273-285.
[56]Irion S,Nostro MC,Kattman SJ,et al.Directed differentiation of pluripotent stem cells:from developmental biology to therapeutic applications.Cold Spring Harb Symp Quant Biol.2008;73:101-110.
[57]Zhu H,Lensch MW,Cahan P,et al.Investigating monogenic and complex diseases with pluripotent stem cells.Nat Rev Genet.2011;12(4):266-275.
[58]Kim C,Wong J,Wen J,et al.Studying arrhythmogenic right ventricular dysplasia with patient-specific i PSCs.Nature.2013;494(7435):105-110.
[59]Spence JR,Mayhew CN,Rankin SA,et al.Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro.Nature.2011;470(7332):105-109.
[60]Takebe T,Sekine K,Enomura M,et al.Vascularized and functional human liver from an i PSC-derived organ bud transplant.Nature.2013;499(7459):481-484.
