Clinical and Experimental Reproductive Medicine

  • 제38권4호
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  • Pages.216-221
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  • 2011
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  • 2233-8233(pISSN)
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  • 2233-8241(eISSN)
대한생식의학회 (The Korean Society for Reproductive Medicine)
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Subretinal transplantation of putative retinal pigment epithelial cells derived from human embryonic stem cells in rat retinal degeneration model

  • Park, Un-Chul (Department of Ophthalmology, Seoul National University College of Medicine) ;
  • Cho, Myung-Soo (Institute of Reproductive Medicine and Population, Medical Research Center, Seoul National University) ;
  • Park, Jung-Hyun (Department of Ophthalmology, Seoul Paik Hospital, Inje University) ;
  • Kim, Sang-Jin (Department of Ophthalmology, Seoul National University College of Medicine) ;
  • Ku, Seung-Yup (Institute of Reproductive Medicine and Population, Medical Research Center, Seoul National University) ;
  • Choi, Young-Min (Institute of Reproductive Medicine and Population, Medical Research Center, Seoul National University) ;
  • Moon, Shin-Yong (Institute of Reproductive Medicine and Population, Medical Research Center, Seoul National University) ;
  • Yu, Hyeong-Gon (Department of Ophthalmology, Seoul National University College of Medicine)
  • 투고 : 2011.09.06
  • 심사 : 2011.12.06
  • 발행 : 2011.12.31
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초록

Objective: To differentiate the human embryonic stem cells (hESCs) into the retinal pigment epithelium (RPE) in the defined culture condition and determine its therapeutic potential for the treatment of retinal degenerative diseases. Methods: The embryoid bodies were formed from hESCs and attached on the matrigel coated culture dishes. The neural structures consisting neural precursors were selected and expanded to form rosette structures. The mechanically isolated neural rosettes were differentiated into pigmented cells in the media comprised of N2 and B27. Expression profiles of markers related to RPE development were analyzed by reverse transcription-polymerase chain reaction and immunostaining. Dissociated putative RPE cells ($10^5$ cells/5 ${\mu}L$) were transplanted into the subretinal space of rat retinal degeneration model induced by intravenous sodium iodate injection. Animals were sacrificed at 1, 2, and 4 weeks after transplantation, and immnohistochemistry study was performed to verify the survival of the transplanted cells. Results: The putative RPE cells derived from hESC showed characteristics of the human RPE cells morphologically and expressed molecular markers and associated with RPE fate. Grafted RPE cells were found to survive in the subretinal space up to 4 weeks after transplantation, and the expression of RPE markers was confirmed with immunohistochemistry. Conclusion: Transplanted RPE cells derived from hESC in the defined culture condition successfully survived and migrated within subretinal space of rat retinal degeneration model. These results support the feasibility of the hESC derived RPE cells for cell-based therapies for retinal degenerative disease.

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참고문헌

  1. Zarbin MA. Current concepts in the pathogenesis of age-related macular degeneration. Arch Ophthalmol 2004;122:598-614. https://doi.org/10.1001/archopht.122.4.598
  2. Strauss O. The retinal pigment epithelium in visual function. Physiol Rev 2005;85:845-81. https://doi.org/10.1152/physrev.00021.2004
  3. Radtke ND, Aramant RB, Petry HM, Green PT, Pidwell DJ, Seiler MJ. Vision improvement in retinal degeneration patients by implantation of retina together with retinal pigment epithelium. Am J Ophthalmol 2008;146:172-82. https://doi.org/10.1016/j.ajo.2008.04.009
  4. Tezel TH, Del Priore LV, Berger AS, Kaplan HJ. Adult retinal pigment epithelial transplantation in exudative age-related macular degeneration. Am J Ophthalmol 2007;143:584-95. https://doi.org/10.1016/j.ajo.2006.12.007
  5. Stanga PE, Kychenthal A, Fitzke FW, Halfyard AS, Chan R, Bird AC, et al. Retinal pigment epithelium translocation after choroidal neovascular membrane removal in age-related macular degeneration. Ophthalmology 2002;109:1492-8. https://doi.org/10.1016/S0161-6420(02)01099-0
  6. Lund RD, Wang S, Klimanskaya I, Holmes T, Ramos-Kelsey R, Lu B, et al. Human embryonic stem cell-derived cells rescue visual function in dystrophic RCS rats. Cloning Stem Cells 2006;8:189-99. https://doi.org/10.1089/clo.2006.8.189
  7. Radtke ND, Seiler MJ, Aramant RB, Petry HM, Pidwell DJ. Transplantation of intact sheets of fetal neural retina with its retinal pigment epithelium in retinitis pigmentosa patients. Am J Ophthalmol 2002;133:544-50. https://doi.org/10.1016/S0002-9394(02)01322-3
  8. Klassen H, Kiilgaard JF, Zahir T, Ziaeian B, Kirov I, Scherfig E, et al. Progenitor cells from the porcine neural retina express photoreceptor markers after transplantation to the subretinal space of allorecipients. Stem Cells 2007;25:1222-30. https://doi.org/10.1634/stemcells.2006-0541
  9. Hoffman LM, Carpenter MK. Characterization and culture of human embryonic stem cells. Nat Biotechnol 2005;23:699-708. https://doi.org/10.1038/nbt1102
  10. Vugler A, Carr AJ, Lawrence J, Chen LL, Burrell K, Wright A, et al. Elucidating the phenomenon of HESC-derived RPE: anatomy of cell genesis, expansion and retinal transplantation. Exp Neurol 2008;214:347-61. https://doi.org/10.1016/j.expneurol.2008.09.007
  11. Klimanskaya I, Hipp J, Rezai KA, West M, Atala A, Lanza R. Derivation and comparative assessment of retinal pigment epithelium from human embryonic stem cells using transcriptomics. Cloning Stem Cells 2004;6:217-45. https://doi.org/10.1089/clo.2004.6.217
  12. Osakada F, Ikeda H, Mandai M, Wataya T, Watanabe K, Yoshimura N, et al. Toward the generation of rod and cone photoreceptors from mouse, monkey and human embryonic stem cells. Nat Biotechnol 2008;26:215-24. https://doi.org/10.1038/nbt1384
  13. Aoki H, Hara A, Nakagawa S, Motohashi T, Hirano M, Takahashi Y, et al. Embryonic stem cells that differentiate into RPE cell precursors in vitro develop into RPE cell monolayers in vivo. Exp Eye Res 2006;82:265-74. https://doi.org/10.1016/j.exer.2005.06.021
  14. Haruta M, Sasai Y, Kawasaki H, Amemiya K, Ooto S, Kitada M, et al. In vitro and in vivo characterization of pigment epithelial cells differentiated from primate embryonic stem cells. Invest Ophthalmol Vis Sci 2004;45:1020-5. https://doi.org/10.1167/iovs.03-1034
  15. Lu B, Malcuit C, Wang S, Girman S, Francis P, Lemieux L, et al. Longterm safety and function of RPE from human embryonic stem cells in preclinical models of macular degeneration. Stem Cells 2009;27:2126-35. https://doi.org/10.1002/stem.149
  16. Idelson M, Alper R, Obolensky A, Ben-Shushan E, Hemo I, Yachimovich-Cohen N, et al. Directed differentiation of human embryonic stem cells into functional retinal pigment epithelium cells. Cell Stem Cell 2009;5:396-408. https://doi.org/10.1016/j.stem.2009.07.002
  17. Oh SK, Kim HS, Ahn HJ, Seol HW, Kim YY, Park YB, et al. Derivation and characterization of new human embryonic stem cell lines: SNUhES1, SNUhES2, and SNUhES3. Stem Cells 2005;23:211-9. https://doi.org/10.1634/stemcells.2004-0122
  18. Cho MS, Lee YE, Kim JY, Chung S, Cho YH, Kim DS, et al. Highly efficient and large-scale generation of functional dopamine neurons from human embryonic stem cells. Proc Natl Acad Sci U S A 2008;105:3392-7. https://doi.org/10.1073/pnas.0712359105
  19. Bjorklund LM, Sanchez-Pernaute R, Chung S, Andersson T, Chen IY, McNaught KS, et al. Embryonic stem cells develop into functional dopaminergic neurons after transplant ation in a Parkinson rat model. Proc Natl Acad Sci U S A 2002;99:2344-9. https://doi.org/10.1073/pnas.022438099
  20. Kim JH, Auerbach JM, Rodriguez-Gomez JA, Velasco I, Gavin D, Lumelsky N, et al. Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease. Nature 2002;418:50-6. https://doi.org/10.1038/nature00900
  21. Takagi Y, Takahashi J, Saiki H, Morizane A, Hayashi T, Kishi Y, et al. Dopaminergic neurons generated from monkey embryonic stem cells function in a Parkinson primate model. J Clin Invest 2005;115:102-9. https://doi.org/10.1172/JCI21137
  22. Sanchez-Pernaute R, Studer L, Ferrari D, Perrier A, Lee H, Vinuela A, et al. Long-term survival of dopamine neurons derived from parthenogenetic primate embryonic stem cells (cyno-1) after transplantation. Stem Cells 2005;23:914-22. https://doi.org/10.1634/stemcells.2004-0172
  23. Vugler A, Lawrence J, Walsh J, Carr A, Gias C, Semo M, et al. Embryonic stem cells and retinal repair. Mech Dev 2007;124:807-29. https://doi.org/10.1016/j.mod.2007.08.002
  24. Cho MS, Hwang DY, Kim DW. Efficient derivation of functional dopaminergic neurons from human embryonic stem cells on a large scale. Nat Protoc 2008;3:1888-94. https://doi.org/10.1038/nprot.2008.188
  25. Banin E, Obolensky A, Idelson M, Hemo I, Reinhardtz E, Pikarsky E, et al. Retinal incorporation and differentiation of neural precursors derived from human embryonic stem cells. Stem Cells 2006;24:246- 57. https://doi.org/10.1634/stemcells.2005-0009
  26. Sakaguchi DS, Van Hoffelen SJ, Theusch E, Parker E, Orasky J, Harper MM, et al. Transplantation of neural progenitor cells into the developing retina of the Brazilian opossum: an in vivo system for studying stem/progenitor cell plasticity. Dev Neurosci 2004;26:336-45. https://doi.org/10.1159/000082275
  27. Coles BL, Angenieux B, Inoue T, Del Rio-Tsonis K, Spence JR, Mc-Innes RR, et al. Facile isolation and the characterization of human retinal stem cells. Proc Natl Acad Sci U S A 2004;101:15772-7. https://doi.org/10.1073/pnas.0401596101
  28. Thomas BB, Samant DM, Seiler MJ, Aramant RB, Sheikholeslami S, Zhang K, et al. Behavioral evaluation of visual function of rats using a visual discrimination apparatus. J Neurosci Methods 2007;162:84-90. https://doi.org/10.1016/j.jneumeth.2006.12.010
  29. Prusky GT, Alam NM, Beekman S, Douglas RM. Rapid quantification of adult and developing mouse spatial vision using a virtual optomotor system. Invest Ophthalmol Vis Sci 2004;45:4611-6. https://doi.org/10.1167/iovs.04-0541
  30. LaVail MM, Sidman RL, Gerhardt CO. Congenic strains of RCS rats with inherited retinal dystrophy. J Hered 1975;66:242-4. https://doi.org/10.1093/oxfordjournals.jhered.a108621

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  2. Recent Advances towards the Clinical Application of Stem Cells for Retinal Regeneration vol.1, pp.4, 2011, https://doi.org/10.3390/cells1040851
  3. Enhancing RPE Cell-Based Therapy Outcomes for AMD: The Role of Bruch's Membrane vol.3, pp.4, 2011, https://doi.org/10.1167/tvst.3.4.4
  4. Stem cell therapies for age-related macular degeneration: the past, present, and future vol.10, pp.None, 2015, https://doi.org/10.2147/cia.s73705
  5. Assessment of Safety and Functional Efficacy of Stem Cell-Based Therapeutic Approaches Using Retinal Degenerative Animal Models vol.2017, pp.None, 2011, https://doi.org/10.1155/2017/9428176
  6. Stem cells in regenerative medicine – from laboratory to clinical application – the eye vol.42, pp.2, 2017, https://doi.org/10.5114/ceji.2017.69360
  7. A new immunodeficient retinal dystrophic rat model for transplantation studies using human-derived cells vol.256, pp.11, 2011, https://doi.org/10.1007/s00417-018-4134-2
  8. Development of 3D Printed Bruch’s Membrane-Mimetic Substance for the Maturation of Retinal Pigment Epithelial Cells vol.22, pp.3, 2021, https://doi.org/10.3390/ijms22031095