诱导多能干细胞分化成视网膜色素上皮细胞的研究进展_Chinese Journal of Ocular Fundus Diseases

Authors：

李扬 ,  马翔 , 卢建民

116044 大连医科大学附属第一医院眼科;

Corresponding author：

马翔, Email: 631949012@qq.com

Keywords：

多能干细胞; 视网膜色素上皮; 细胞分化; 综述

DOI：

10.3760/cma.j.issn.1005-1015.2015.02.031

Video：

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Abstract Full text Figures/Tables Video References Cited by

干细胞起源的视网膜色素上皮(RPE)细胞是治疗视网膜变性性疾病的种子资源。诱导多能干细胞(iPSC)是与胚胎干细胞有相似性质的干细胞, 可分化为RPE细胞。目前眼科领域对iPSCs的研究仅停留在动物实验及体外实验阶段。对iPSCs的深入研究可拓展其应用前景, 为视网膜变性性疾病的治疗提供新的思路和方法。

Citation： 李扬, 马翔, 卢建民. 诱导多能干细胞分化成视网膜色素上皮细胞的研究进展. Chinese Journal of Ocular Fundus Diseases, 2015, 31(2): 212-214. doi: 10.3760/cma.j.issn.1005-1015.2015.02.031 Copy

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2.	Lund RD, Wang S, Klimanskaya I, et al. Human embryonic stem cellderived cells rescue visual function in dystrophic RCS rats[J]. Cloning Stem Cells, 2006, 8(3):189-199.
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4.	Vugler A, Carr AJ, Lawrence J, et al. Elucidating the phenomenon of HESC-derived RPE:anatomy of cell genesis, expansion and retinal transplantation[J]. Exp Neurol, 2008, 214(2):347-361.
5.	Gong J, Sagiv O, Cai H, et al. Effects of extracellular matrix and neighboring cells on induction of human embryonic stem cells into retinal or retinal pigment epithelial progenitors[J]. Exp Eye Res, 2008, 86(6):957-965.
6.	Vugler A, Lawrence J, Walsh J, et al. Embryonic stem cells and retinal repair[J]. Mech Dev, 2007, 124(11-12):807-829.
7.	Takahashi K, Yamanaka S.Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors[J]. Cell, 2006, 126(4):663-676.
8.	Maherali N, Sridharan R, Xie W, et al.Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution[J]. Cell Stem Cell, 2007, 1(1):55-70.
9.	Wernig M, Meissner A, Foreman R, et al.In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state[J]. Nature, 2007, 448(7151):318-324.
10.	Lowry WE, Richter L, Yachechko R, et al.Generation of human induced pluripotent stem cells from dermal fibroblasts[J]. Proc Natl Acad Sci USA, 2008, 105(8):2883-2888.
11.	Park IH, Zhao R, West JA, et al.Reprogramming of human somatic cells to pluripotency with defined factors[J]. Nature, 2008, 451(7175):141-146.
12.	Takahashi K, Tanabe K, Ohnuki M, et al.Induction of pluripotent stem cells from adult human fibroblasts by defined factors[J].Cell, 2007, 131(5):861-872.
13.	Yu J, Vodyanik MA, Smuga-Otto K, et al.Induced pluripotent stem cell lines derived from human somatic cells[J]. Science, 2007, 318(5858):1917-1920.
14.	Nakagawa M, Koyanagi M, Tanabe K, et al. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts[J]. Nat Biotechnol, 2008, 26(1):101-106.
15.	Klopsch C, Donndorf P, Kaminski A, et al. Cell sources for cardiovascular tissue engineering[J]. Chirurg, 2011, 82(4):295-302.
16.	Feng B, Jiang J, Kraus P, et al.Reprogramming of fibroblasts into induced pluripotent stem cells with orphan nuclear receptor Esrrb[J]. Nat Cell Biol, 2009, 11(2):197-203.
17.	Lyssiotis CA, Foreman RK, Staerk J, et al.Reprogramming of murine fibroblasts to induced pluripotent stem cells with chemical complementation of Klf4[J]. Proc Natl Acad Sci USA, 2009, 106(22):8912-8917.
18.	Wernig M, Meissner A, Cassady JP, et al. c-Myc is dispensable for direct reprogramming of mouse fibroblasts[J]. Cell Stem Cell, 2008, 2(1):10-12.
19.	Marson A, Foreman R, Chevalier B, et al.Wnt signaling promotes reprogramming of somatic cells to pluripotency[J].Cell Stem Cell, 2008(2), 3:132-135.
20.	Huangfu D, Maehr R, Guo W, et al.Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds[J]. Nat Biotechnol, 2008, 26(7):795-797.
21.	Mikkelsen TS, Hanna J, Zhang X, et al.Dissecting direct reprogramming through integrative genomic analysis[J]. Nature, 2008, 454(7200):49-55.
22.	Shi Y, Desponts C, Do JT, et al.Induction of pluripotent stem cells from mouse embryonic fi broblasts by Oct4 and Klf4 with small-molecule compounds[J]. Cell Stem Cell, 2008, 3(5):568-574.
23.	Hacein-Bey-Abina S, von Kalle C, Schmidt M, et al.LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1[J]. Science, 2003, 302(5644):415-419.
24.	Aoi T, Yae K, Nakagawa M, et al. Generation of pluripotent stem cells from adult mouse liver and stomach cells[J].Science, 2008, 321(5889):699-702.
25.	Zhao T, Zhang ZN, Rong Z, et al. Immunogenicity of induced pluripotent stem cells[J]. Nature, 2011, 474(7350):212-215.
26.	Okita K, Nakagawa M, Hyenjong H, et al.Generation of mouse induced pluripotent stem cells without viral vectors[J].Science, 2008, 322(5903):949-953.
27.	Fusaki N, Ban H, Nishiyama A, et al. Efficient induction of transgene-free human pluripotent stem cells using a vector based on Sendai virus, an RNA virus that does not integrate into the host genome[J]. Proc Jpn Acad Ser B Phys Biol Sci, 2009, 85(8):348-362.
28.	Stadtfeld M, Nagaya M, Utikal J, et al.Induced pluripotent stem cells generated without viral integration[J]. Science, 2008, 322(5903):945-949.
29.	Warren L, Manos PD, Ahfeldt T, et al. Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA[J]. Cell Stem Cell, 2010, 7(5):618-630.
30.	Maherali N, Hochedlinger K.Guidelines and techniques for the generation of induced pluripotent stem cells[J].Cell Stem Cell, 2008, 3(6):595-605.
31.	Thomson JA, Itskovitz-Eldor J, Shapiro SS, et al. Embryonic stem cell lines derived from human blastocysts[J]. Science, 1998, 282(5391):1145-1147.
32.	Xu C, Inokuma MS, Denham J, et al.Feeder-free growth of undifferentiated human embryonic stem cells[J].Nat Biotechnol, 2001, 19(10):971-974.
33.	Richards M, Fong CY, Chan WK, et al.Human feeders support prolonged undifferentiated growth of human inner cell masses and embryonic stem cells[J]. Nat Biotechnol, 2002, 20(9):933-936.
34.	Amit M, Shariki C, Margulets V, et al.Feeder layer-and serum-free culture of human embryonic stem cells[J].Biol Reprod, 2004, 70(3):837-845.
35.	Reubinoff BE, Pera MF, Fong CY, et al.Embryonic stem cell lines from human blastocysts:somatic differentiation in vitro[J]. Nat Biotechnol, 2000, 18(4):399-404.
36.	Cowan CA, Klimanskaya I, McMahon J, et al.Derivation of embryonic stem-cell lines from human blastocysts[J]. N Engl J Med, 2004, 350(13):1353-1356.
37.	Oh SK, Kim HS, Park YB, et al.Methods for expansion of human embryonic stem cells[J]. Stem Cells, 2005, 23(5):605-609.
38.	Hoffman LM, Carpenter MK.Characterization and culture of human embryonic stem cells[J]. Nat Biotechnol, 2005, 23(6):699-708.
39.	Hohenstein Elliott KA, Peterson C, Soundararajan A, et al. Laser-based propagation of human ips and es cells generates reproducible cultures with enhanced differentiation potential. Stem Cells Int. 2012, 2012:926463. http//www.hindawi.com/journals/sci/2012/926463/..
40.	Osakada F, Ikeda H, Sasai Y, et al. Stepwise differentiation of pluripotent stem cells intoretinal cells[J]. Nat Protoc, 2009, 4(6):811-824.
41.	Corneo B, Temple S. Sense and serendipity aid RPE generation[J]. Cell Stem Cell, 2009, 5(4):347-348.
42.	Lund RD, Wang S, Klimanskaya I, et al.Human embruonic stem cell-derived cells rescue visual function in dystrophic RCS rats[J].Cloning Stem Cells, 2006, 8 (3):189-199.
43.	Lu B, Malcuit C, Wang S, et al. Long-term safety and function of RPE from human embryonic stem cells in preclinical models of macular degeneration[J]. Stem Cells, 2009, 27(9):2126-2135.
44.	Lamba DA, Karl MO, Ware CB, et al. Efficient generation of retinal progenitor cells from human embryonic stem cells[J]. Proc Natl Acad Sci USA, 2006, 103(34):12769-12774.
45.	Liu Y, Gao L, Zuba-Surma EK.et al.Identification of small Sca-1(+), Lin(-), CD45(-) multipotential cells in the neonatal murine retina[J].Exp Hematol, 2009, 37(9):1096-1107.
46.	Hu BY, Weick JP, Yu J, et al.Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency[J].Proc Natl Acad Sci USA, 2010, 107(9):4335-4340.
47.	Junying M, Kejin H, Kim SO, et al.Human induced pluripotent stem cells free of vector and transgene sequences[J].Science, 2009, 324(5928):797-801.
48.	Meyer JS, Howden SE, Wallace KA, et al.Optic vesicle-like structures derived from human pluripotent stem cells facilitate a customized approach to retinal disease treatment[J].Stem Cells, 2011, 29(8):1206-1218.
49.	Osakada F, Jin ZB, Hirami Y, et al. In vitro differentiation of retinal cells from human pluripotent stem cells by small-molecule induction[J]. J Cell Sci, 2009, 122(Pt 17):3169-3179.
50.	Jin ZB, Okamoto S, Mandai M, et al. Induced pluripotent stem cells for retinal degenerative diseases:a new perspective on the challenges[J]. J Genet, 2009, 88(4):417-424.
51.	Meyer JS, Shearter RL, Capowski EE, et al. Modeling early retinal development with human embryonic and induced pluripotent stem cells[J].Proc Natl Acad Sci USA, 2009, 106(39):16698-16703.
52.	Osakada F, Ikeda H, Sasai Y, et al. Stepwise differentiation of pluripotent stem cells into retinal cells[J]. Nat Protoc, 2009, 4(6):811-824.
53.	Parameswaran S, Balasubramanian S, Babai N, et al. Induced pluripotent stem cells generate both retinal ganglion cells and photoreceptors:therapeutic implications in degenerative changes in glaucoma and age-related macular degeneration[J].Stem Cells, 2010:28(4):695-703.
54.	Hirami Y, Osakada F, Takahashi K, et al.Generation of retinal cells from mouse and human induced pluripotent stem cells[J]. Neurosci Lett, 2009, 458(3):126-131.
55.	Carr AJ, Vugler AA, Hikita ST, et al. Protective effects of human iPS-derived retinal pigment epithelium celltransplantation in the retinal dystrophic rat.PLoS One, 2009, 4(12):8152.http://eprints.ucl.ac.uk/141340/1/141340.pdf..
56.	Okamoto S, Takahashi M. Induction of retinal pigment epithelial cells from monkey iPS cells[J]. Invest Ophthalmol Vis Sci, 2011, 52(12):8785-8790.
57.	Mekala SR, Vauhini V, Nagarajan U, et al.Derivation, characterization and retinal differentiation of induced pluripotent stem cells[J]. J Biosci, 2013, 38(1):123-134.
58.	Cyranoski D. Stem cells cruise to clinic[J]. Nature, 2013, 494(7438):413.
59.	Chin MH, Mason MJ, Xie W, et al. Induced pluripotent stem cells and embryonic stem cells are distinguished by gene expression signatures[J].Cell Stem Cell, 2009, 5(1):111-123.
60.	Kim JB, Zaehres H, Wu G, et al. Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors[J].Nature, 2008, 454(7204):646-650.
61.	Miura K, Okada Y, Aoi T, et al. Variation in the safety of induced pluripotent stem cell lines[J].Nat Biotechnol, 2009, 27(8):743-745.
62.	Niemann H, Tian XC, King WA, et al. Epigenetic reprogramming in embryonic and foetal development upon somatic cell nuclear transfer cloning[J]. Reproduction, 2008, 135(2):151-163.
63.	吴佳慧, 崔红平.iPSCs在眼科疾病的研究进展[J].国际眼科杂志, 2013, 13(2):295-298.

1. Klimanskaya I, Hipp J, Rezai KA, et al. Derivation and comparative assessment of retinal pigment epithelium from human embryonic stem cells using transcriptomics[J]. Cloning Stem Cells, 2004, 6(3):217-245.
2. Lund RD, Wang S, Klimanskaya I, et al. Human embryonic stem cellderived cells rescue visual function in dystrophic RCS rats[J]. Cloning Stem Cells, 2006, 8(3):189-199.
3. Carr AJ, Vugler A, Lawrence J, et al. Molecular characterization and functional analysis of phagocytosis by human embryonic stem cellderived RPE cells using a novel human retinal assay[J]. Mol Vis, 2009, 15:283-295.
4. Vugler A, Carr AJ, Lawrence J, et al. Elucidating the phenomenon of HESC-derived RPE:anatomy of cell genesis, expansion and retinal transplantation[J]. Exp Neurol, 2008, 214(2):347-361.
5. Gong J, Sagiv O, Cai H, et al. Effects of extracellular matrix and neighboring cells on induction of human embryonic stem cells into retinal or retinal pigment epithelial progenitors[J]. Exp Eye Res, 2008, 86(6):957-965.
6. Vugler A, Lawrence J, Walsh J, et al. Embryonic stem cells and retinal repair[J]. Mech Dev, 2007, 124(11-12):807-829.
7. Takahashi K, Yamanaka S.Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors[J]. Cell, 2006, 126(4):663-676.
8. Maherali N, Sridharan R, Xie W, et al.Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution[J]. Cell Stem Cell, 2007, 1(1):55-70.
9. Wernig M, Meissner A, Foreman R, et al.In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state[J]. Nature, 2007, 448(7151):318-324.
10. Lowry WE, Richter L, Yachechko R, et al.Generation of human induced pluripotent stem cells from dermal fibroblasts[J]. Proc Natl Acad Sci USA, 2008, 105(8):2883-2888.
11. Park IH, Zhao R, West JA, et al.Reprogramming of human somatic cells to pluripotency with defined factors[J]. Nature, 2008, 451(7175):141-146.
12. Takahashi K, Tanabe K, Ohnuki M, et al.Induction of pluripotent stem cells from adult human fibroblasts by defined factors[J].Cell, 2007, 131(5):861-872.
13. Yu J, Vodyanik MA, Smuga-Otto K, et al.Induced pluripotent stem cell lines derived from human somatic cells[J]. Science, 2007, 318(5858):1917-1920.
14. Nakagawa M, Koyanagi M, Tanabe K, et al. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts[J]. Nat Biotechnol, 2008, 26(1):101-106.
15. Klopsch C, Donndorf P, Kaminski A, et al. Cell sources for cardiovascular tissue engineering[J]. Chirurg, 2011, 82(4):295-302.
16. Feng B, Jiang J, Kraus P, et al.Reprogramming of fibroblasts into induced pluripotent stem cells with orphan nuclear receptor Esrrb[J]. Nat Cell Biol, 2009, 11(2):197-203.
17. Lyssiotis CA, Foreman RK, Staerk J, et al.Reprogramming of murine fibroblasts to induced pluripotent stem cells with chemical complementation of Klf4[J]. Proc Natl Acad Sci USA, 2009, 106(22):8912-8917.
18. Wernig M, Meissner A, Cassady JP, et al. c-Myc is dispensable for direct reprogramming of mouse fibroblasts[J]. Cell Stem Cell, 2008, 2(1):10-12.
19. Marson A, Foreman R, Chevalier B, et al.Wnt signaling promotes reprogramming of somatic cells to pluripotency[J].Cell Stem Cell, 2008(2), 3:132-135.
20. Huangfu D, Maehr R, Guo W, et al.Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds[J]. Nat Biotechnol, 2008, 26(7):795-797.
21. Mikkelsen TS, Hanna J, Zhang X, et al.Dissecting direct reprogramming through integrative genomic analysis[J]. Nature, 2008, 454(7200):49-55.
22. Shi Y, Desponts C, Do JT, et al.Induction of pluripotent stem cells from mouse embryonic fi broblasts by Oct4 and Klf4 with small-molecule compounds[J]. Cell Stem Cell, 2008, 3(5):568-574.
23. Hacein-Bey-Abina S, von Kalle C, Schmidt M, et al.LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1[J]. Science, 2003, 302(5644):415-419.
24. Aoi T, Yae K, Nakagawa M, et al. Generation of pluripotent stem cells from adult mouse liver and stomach cells[J].Science, 2008, 321(5889):699-702.
25. Zhao T, Zhang ZN, Rong Z, et al. Immunogenicity of induced pluripotent stem cells[J]. Nature, 2011, 474(7350):212-215.
26. Okita K, Nakagawa M, Hyenjong H, et al.Generation of mouse induced pluripotent stem cells without viral vectors[J].Science, 2008, 322(5903):949-953.
27. Fusaki N, Ban H, Nishiyama A, et al. Efficient induction of transgene-free human pluripotent stem cells using a vector based on Sendai virus, an RNA virus that does not integrate into the host genome[J]. Proc Jpn Acad Ser B Phys Biol Sci, 2009, 85(8):348-362.
28. Stadtfeld M, Nagaya M, Utikal J, et al.Induced pluripotent stem cells generated without viral integration[J]. Science, 2008, 322(5903):945-949.
29. Warren L, Manos PD, Ahfeldt T, et al. Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA[J]. Cell Stem Cell, 2010, 7(5):618-630.
30. Maherali N, Hochedlinger K.Guidelines and techniques for the generation of induced pluripotent stem cells[J].Cell Stem Cell, 2008, 3(6):595-605.
31. Thomson JA, Itskovitz-Eldor J, Shapiro SS, et al. Embryonic stem cell lines derived from human blastocysts[J]. Science, 1998, 282(5391):1145-1147.
32. Xu C, Inokuma MS, Denham J, et al.Feeder-free growth of undifferentiated human embryonic stem cells[J].Nat Biotechnol, 2001, 19(10):971-974.
33. Richards M, Fong CY, Chan WK, et al.Human feeders support prolonged undifferentiated growth of human inner cell masses and embryonic stem cells[J]. Nat Biotechnol, 2002, 20(9):933-936.
34. Amit M, Shariki C, Margulets V, et al.Feeder layer-and serum-free culture of human embryonic stem cells[J].Biol Reprod, 2004, 70(3):837-845.
35. Reubinoff BE, Pera MF, Fong CY, et al.Embryonic stem cell lines from human blastocysts:somatic differentiation in vitro[J]. Nat Biotechnol, 2000, 18(4):399-404.
36. Cowan CA, Klimanskaya I, McMahon J, et al.Derivation of embryonic stem-cell lines from human blastocysts[J]. N Engl J Med, 2004, 350(13):1353-1356.
37. Oh SK, Kim HS, Park YB, et al.Methods for expansion of human embryonic stem cells[J]. Stem Cells, 2005, 23(5):605-609.
38. Hoffman LM, Carpenter MK.Characterization and culture of human embryonic stem cells[J]. Nat Biotechnol, 2005, 23(6):699-708.
39. Hohenstein Elliott KA, Peterson C, Soundararajan A, et al. Laser-based propagation of human ips and es cells generates reproducible cultures with enhanced differentiation potential. Stem Cells Int. 2012, 2012:926463. http//www.hindawi.com/journals/sci/2012/926463/..
40. Osakada F, Ikeda H, Sasai Y, et al. Stepwise differentiation of pluripotent stem cells intoretinal cells[J]. Nat Protoc, 2009, 4(6):811-824.
41. Corneo B, Temple S. Sense and serendipity aid RPE generation[J]. Cell Stem Cell, 2009, 5(4):347-348.
42. Lund RD, Wang S, Klimanskaya I, et al.Human embruonic stem cell-derived cells rescue visual function in dystrophic RCS rats[J].Cloning Stem Cells, 2006, 8 (3):189-199.
43. Lu B, Malcuit C, Wang S, et al. Long-term safety and function of RPE from human embryonic stem cells in preclinical models of macular degeneration[J]. Stem Cells, 2009, 27(9):2126-2135.
44. Lamba DA, Karl MO, Ware CB, et al. Efficient generation of retinal progenitor cells from human embryonic stem cells[J]. Proc Natl Acad Sci USA, 2006, 103(34):12769-12774.
45. Liu Y, Gao L, Zuba-Surma EK.et al.Identification of small Sca-1(+), Lin(-), CD45(-) multipotential cells in the neonatal murine retina[J].Exp Hematol, 2009, 37(9):1096-1107.
46. Hu BY, Weick JP, Yu J, et al.Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency[J].Proc Natl Acad Sci USA, 2010, 107(9):4335-4340.
47. Junying M, Kejin H, Kim SO, et al.Human induced pluripotent stem cells free of vector and transgene sequences[J].Science, 2009, 324(5928):797-801.
48. Meyer JS, Howden SE, Wallace KA, et al.Optic vesicle-like structures derived from human pluripotent stem cells facilitate a customized approach to retinal disease treatment[J].Stem Cells, 2011, 29(8):1206-1218.
49. Osakada F, Jin ZB, Hirami Y, et al. In vitro differentiation of retinal cells from human pluripotent stem cells by small-molecule induction[J]. J Cell Sci, 2009, 122(Pt 17):3169-3179.
50. Jin ZB, Okamoto S, Mandai M, et al. Induced pluripotent stem cells for retinal degenerative diseases:a new perspective on the challenges[J]. J Genet, 2009, 88(4):417-424.
51. Meyer JS, Shearter RL, Capowski EE, et al. Modeling early retinal development with human embryonic and induced pluripotent stem cells[J].Proc Natl Acad Sci USA, 2009, 106(39):16698-16703.
52. Osakada F, Ikeda H, Sasai Y, et al. Stepwise differentiation of pluripotent stem cells into retinal cells[J]. Nat Protoc, 2009, 4(6):811-824.
53. Parameswaran S, Balasubramanian S, Babai N, et al. Induced pluripotent stem cells generate both retinal ganglion cells and photoreceptors:therapeutic implications in degenerative changes in glaucoma and age-related macular degeneration[J].Stem Cells, 2010:28(4):695-703.
54. Hirami Y, Osakada F, Takahashi K, et al.Generation of retinal cells from mouse and human induced pluripotent stem cells[J]. Neurosci Lett, 2009, 458(3):126-131.
55. Carr AJ, Vugler AA, Hikita ST, et al. Protective effects of human iPS-derived retinal pigment epithelium celltransplantation in the retinal dystrophic rat.PLoS One, 2009, 4(12):8152.http://eprints.ucl.ac.uk/141340/1/141340.pdf..
56. Okamoto S, Takahashi M. Induction of retinal pigment epithelial cells from monkey iPS cells[J]. Invest Ophthalmol Vis Sci, 2011, 52(12):8785-8790.
57. Mekala SR, Vauhini V, Nagarajan U, et al.Derivation, characterization and retinal differentiation of induced pluripotent stem cells[J]. J Biosci, 2013, 38(1):123-134.
58. Cyranoski D. Stem cells cruise to clinic[J]. Nature, 2013, 494(7438):413.
59. Chin MH, Mason MJ, Xie W, et al. Induced pluripotent stem cells and embryonic stem cells are distinguished by gene expression signatures[J].Cell Stem Cell, 2009, 5(1):111-123.
60. Kim JB, Zaehres H, Wu G, et al. Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors[J].Nature, 2008, 454(7204):646-650.
61. Miura K, Okada Y, Aoi T, et al. Variation in the safety of induced pluripotent stem cell lines[J].Nat Biotechnol, 2009, 27(8):743-745.
62. Niemann H, Tian XC, King WA, et al. Epigenetic reprogramming in embryonic and foetal development upon somatic cell nuclear transfer cloning[J]. Reproduction, 2008, 135(2):151-163.
63. 吴佳慧, 崔红平.iPSCs在眼科疾病的研究进展[J].国际眼科杂志, 2013, 13(2):295-298.

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诱导多能干细胞分化成视网膜色素上皮细胞的研究进展

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