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Utilizing Stem Cell-Derived RPE Cells as A Therapeutic Intervention for Age-Related Macular Degeneration

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Retinal Degenerative Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 801))

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Abbreviations

RPE:

Retinal pigment epithelium

AMD:

Age-related macular degeneration

iPSC:

Induced pluripotent stem cell

iPSC-RPE:

Induced pluripotent stem cell-derived RPE

hESC:

Human embryonic stem cell

hESC-RPE:

Human embryonic stem cell-derived RPE

HLA:

Human leukocyte antigen

OSKM:

Oct4, Sox2, Klf4, and c-Myc

OSNL:

Oct4, Sox2, Nanog, and Lin28

ACT:

Advanced Cell Technology, Inc

References

  1. Strauss O (2005) The retinal pigment epithelium in visual function. Physiol Rev 85(3):845–881

    Article  PubMed  CAS  Google Scholar 

  2. Congdon N, O’Colmain B, Klaver CC, Klein R, Munoz B, Friedman DS et al (2004) Causes and prevalence of visual impairment among adults in the United States. Arch Ophthalmol 122(4):477–485

    Article  PubMed  Google Scholar 

  3. Resnikoff S, Pascolini D, Etya’ale D, Kocur I, Pararajasegaram R, Pokharel GP et al (2004) Global data on visual impairment in the year 2002. Bull World Health Organ 82(11):844–851

    PubMed Central  PubMed  Google Scholar 

  4. Friedman DS, O’Colmain BJ, Munoz B, Tomany SC, McCarty C, de Jong PT et al (2004) Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol 122(4):564–572

    Article  PubMed  Google Scholar 

  5. Bird AC (2010) Therapeutic targets in age-related macular disease. J Clin Invest 120(9):3033–3041

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  6. Algvere PV, Gouras P, Dafgard Kopp E (1999) Long-term outcome of RPE allografts in non-immunosuppressed patients with AMD. Eur J Ophthalmol 9(3):217–230

    PubMed  CAS  Google Scholar 

  7. Cahill MT, Freedman SF, Toth CA (2003) Macular translocation with 360 degrees peripheral retinectomy for geographic atrophy. Arch Ophthalmol 121(1):132–133

    Article  PubMed  Google Scholar 

  8. Joussen AM, Joeres S, Fawzy N, Heussen FM, Llacer H, van Meurs JC et al (2007) Autologous translocation of the choroid and retinal pigment epithelium in patients with geographic atrophy. Ophthalmology 114(3):551–560

    Article  PubMed  Google Scholar 

  9. Zhang X, Bok D (1998) Transplantation of retinal pigment epithelial cells and immune response in the subretinal space. Invest Ophthalmol Vis Sci 39(6):1021–1027

    PubMed  CAS  Google Scholar 

  10. Marc R (2005) Retinal remodeling. J Vis 5(12):5

    Google Scholar 

  11. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K et al (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131(5):861–872

    Article  PubMed  CAS  Google Scholar 

  12. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S et al (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318(5858):1917–1920

    Article  PubMed  CAS  Google Scholar 

  13. Aoi T, Yae K, Nakagawa M, Ichisaka T, Okita K, Takahashi K et al (2008) Generation of pluripotent stem cells from adult mouse liver and stomach cells. Science 321(5889):699–702

    Article  PubMed  CAS  Google Scholar 

  14. Bock C, Kiskinis E, Verstappen G, Gu H, Boulting G, Smith ZD et al (2011) Reference maps of human ES and iPS cell variation enable high-throughput characterization of pluripotent cell lines. Cell 144(3):439–452

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  15. Hussein SM, Batada NN, Vuoristo S, Ching RW, Autio R, Narva E et al (2011) Copy number variation and selection during reprogramming to pluripotency. Nature 471(7336):58–62

    Article  PubMed  CAS  Google Scholar 

  16. Laurent LC, Ulitsky I, Slavin I, Tran H, Schork A, Morey R et al (2011) Dynamic changes in the copy number of pluripotency and cell proliferation genes in human ESCs and iPSCs during reprogramming and time in culture. Cell Stem Cell 8(1):106–118

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  17. Markoulaki S, Hanna J, Beard C, Carey BW, Cheng AW, Lengner CJ et al (2009) Transgenic mice with defined combinations of drug-inducible reprogramming factors. Nat Biotechnol 27(2):169–171

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  18. Mayshar Y, Ben-David U, Lavon N, Biancotti JC, Yakir B, Clark AT et al (2010) Identification and classification of chromosomal aberrations in human induced pluripotent stem cells. Cell Stem Cell 7(4):521–531

    Article  PubMed  CAS  Google Scholar 

  19. Quinlan AR, Boland MJ, Leibowitz ML, Shumilina S, Pehrson SM, Baldwin KK et al (2011) Genome sequencing of mouse induced pluripotent stem cells reveals retroelement stability and infrequent DNA rearrangement during reprogramming. Cell Stem Cell 9(4):366–373

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  20. Zhao T, Zhang Z-N, Rong Z, Xu Y (2011) Immunogenicity of induced pluripotent stem cells. Nature 474(7350):212–215

    Article  PubMed  CAS  Google Scholar 

  21. Idelson M, Alper R, Obolensky A, Ben-Shushan E, Hemo I, Yachimovich-Cohen N et al (2009) Directed differentiation of human embryonic stem cells into functional retinal pigment epithelium cells. Cell Stem Cell 5(4):396–408

    Article  PubMed  CAS  Google Scholar 

  22. Klimanskaya I, Hipp J, Rezai KA, West M, Atala A, Lanza R (2004) Derivation and comparative assessment of retinal pigment epithelium from human embryonic stem cells using transcriptomics. Cloning Stem Cells 6(3):217–245

    Article  PubMed  CAS  Google Scholar 

  23. Lund RD, Wang S, Klimanskaya I, Holmes T, Ramos-Kelsey R, Lu B et al (2006) Human embryonic stem cell-derived cells rescue visual function in dystrophic RCS rats. Cloning Stem Cells 8(3):189–199

    Article  PubMed  CAS  Google Scholar 

  24. Meyer JS, Shearer RL, Capowski EE, Wright LS, Wallace KA, McMillan EL et al (2009) Modeling early retinal development with human embryonic and induced pluripotent stem cells. Proc Natl Acad Sci 106(39):16698–16703

    Article  PubMed Central  PubMed  Google Scholar 

  25. Vugler A, Carr AJ, Lawrence J, Chen LL, Burrell K, Wright A et al (2008) Elucidating the phenomenon of HESC-derived RPE: anatomy of cell genesis, expansion and retinal transplantation. Exp Neurol 214(2):347–361

    Article  PubMed  CAS  Google Scholar 

  26. Buchholz DE, Hikita ST, Rowland TJ, Friedrich AM, Hinman CR, Johnson LV et al (2009) Derivation of functional retinal pigmented epithelium from induced pluripotent stem cells. Stem Cells 27(10):2427–2434

    Article  PubMed  CAS  Google Scholar 

  27. Carr AJ, Vugler AA, Hikita ST, Lawrence JM, Gias C, Chen LL et al (2009) Protective effects of human iPS-derived retinal pigment epithelium cell transplantation in the retinal dystrophic rat. PLoS One 4(12):e8152

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  28. Hirami Y, Osakada F, Takahashi K, Okita K, Yamanaka S, Ikeda H et al (2009) Generation of retinal cells from mouse and human induced pluripotent stem cells. Neurosci Lett 458(3):126–131

    Article  PubMed  CAS  Google Scholar 

  29. Krohne T, Westenskow P, Kurihara T, Friedlander D, Lehmann M, Dorsey A et al (2012) Generation of retinal pigment epithelial cells from small molecules and OCT4-reprogrammed human induced pluripotent stem cells. Stem Cells Trans Med 1(2):96–109

    Article  CAS  Google Scholar 

  30. Osakada F, Jin ZB, Hirami Y, Ikeda H, Danjyo T, Watanabe K et al (2009) In vitro differentiation of retinal cells from human pluripotent stem cells by small-molecule induction. J Cell Sci 122(Pt 17):3169–3179

    Article  PubMed  CAS  Google Scholar 

  31. Mircheff AK, Miller SS, Farber DB, Bradley ME, O’Day WT, Bok D (1990) Isolation and provisional identification of plasma membrane populations from cultured human retinal pigment epithelium. Invest Ophthalmol Vis Sci 31(5):863–878

    PubMed  CAS  Google Scholar 

  32. Kokkinaki M, Sahibzada N Golestaneh N (2011) Human induced pluripotent stem-derived retinal pigment epithelium (RPE) cells exhibit ion transport, membrane potential, polarized vascular endothelial growth factor secretion, and gene expression pattern similar to native RPE. Stem Cells 29(5):825–835

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  33. Carr AJ, Vugler A, Lawrence J, Chen LL, Ahmado A, Chen FK et al (2009) Molecular characterization and functional analysis of phagocytosis by human embryonic stem cell-derived RPE cells using a novel human retinal assay. Mol Vis 15:283–295

    PubMed Central  PubMed  CAS  Google Scholar 

  34. Westenskow PD, Moreno SK, Krohne TU, Kurihara T, Zhu S, Zhang ZN et al (2012) Using flow cytometry to compare the dynamics of photoreceptor outer segment phagocytosis in iPS-derived RPE cells. Invest Ophthalmol Vis Sci 53(10):6282–6290

    Article  PubMed Central  PubMed  Google Scholar 

  35. Schwartz SD, Hubschman J-P, Heilwell G, Franco-Cardenas V, Pan CK, Ostrick RM et al (2012) Embryonic stem cell trials for macular degeneration: a preliminary report. Lancet 379(9817):713–720

    Article  PubMed  CAS  Google Scholar 

  36. Lu B, Malcuit C, Wang S, Girman S, Francis P, Lemieux L et al (2009) Long-term safety and function of RPE from human embryonic stem cells in preclinical models of macular degeneration. Stem Cells 27(9):2126–2135

    Article  PubMed  CAS  Google Scholar 

  37. Sheridan C, Williams R, Grierson I (2004) Basement membranes and artificial substrates in cell transplantation. Graefes Arch Clin Exp Ophthalmol 242(1):68–75

    Article  PubMed  Google Scholar 

  38. Williams RL, Krishna Y, Dixon S, Haridas A, Grierson I, Sheridan C (2005) Polyurethanes as potential substrates for sub-retinal retinal pigment epithelial cell transplantation. J Mater Sci Mater Med 16(12):1087–1092

    Article  PubMed  CAS  Google Scholar 

  39. Okita K, Ichisaka T, Yamanaka S. 2007 Generation of germline-competent induced pluripotent stem cells. Nature 448(7151):313–317

    Article  PubMed  CAS  Google Scholar 

  40. Karamehic J, Ridic O, Jukic T, Ridic G, Slipicevic O, Coric J et al (2011) Financial aspects of the immunosuppressive therapy. Med Arh 65(6):357–362

    Article  PubMed  Google Scholar 

  41. Tezel TH, Del Priore LV, Berger AS, Kaplan HJ (2007) Adult retinal pigment epithelial transplantation in exudative age-related macular degeneration. Am J Ophthalmol 143(4):584–595

    Article  PubMed  Google Scholar 

  42. Eiraku M, Takata N, Ishibashi H, Kawada M, Sakakura E, Okuda S et al (2011) Self-organizing optic-cup morphogenesis in three-dimensional culture. Nature 472(7341):51–56

    Article  PubMed  CAS  Google Scholar 

  43. Nakano T, Ando S, Takata N, Kawada M, Muguruma K, Sekiguchi K et al (2012) Self-formation of optic cups and storable stratified neural retina from human ESCs. Cell Stem Cell 10(6):771–785

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We wish to warmly thank all members of the Friedlander lab and our collaborators. Work discussed in this chapter was supported by generous funding to PDW, a Ruth Kirschstein Fellow (NEI EY021416), to TK (Manpei Suzuki Diabetes Foundation and The Japan Society for the Promotion of Science Postdoctoral Fellowships for Research Abroad), and to MF from the NEI (EY11254; EY017540), the California Institute for Regenerative Medicine (CIRM TR1–01219), the Lowy Medical Research Foundation (the MacTel Project), and the Rasmussen Foundation.

Author information

Authors and Affiliations

  1. Department of Cell Biology, The Scripps Research Institute, MB 216, 10550 N. Torrey Pines Rd, 92014, La Jolla, CA, USA

    Peter D. Westenskow, Toshihide Kurihara & Martin Friedlander

Authors
  1. Peter D. Westenskow
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  2. Toshihide Kurihara
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  3. Martin Friedlander
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Corresponding author

Correspondence to Martin Friedlander .

Editor information

Editors and Affiliations

  1. Department of Ophthalmology, University of Florida, Gainesville, Florida, USA

    John D. Ash

  2. University Hospital Zurich, Zurich, Switzerland

    Christian Grimm

  3. Cole Eye Institute at the Cleveland Clin Division of Ophthalmology, Cleveland, Ohio, USA

    Joe G. Hollyfield

  4. Dean A. McGee Eye Inst., University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA

    Robert E. Anderson

  5. Beckman Vision Center, University of California, San Francisco School of Medicine, San Francisco, California, USA

    Matthew M. LaVail

  6. Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina, USA

    Catherine Bowes Rickman

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Westenskow, P., Kurihara, T., Friedlander, M. (2014). Utilizing Stem Cell-Derived RPE Cells as A Therapeutic Intervention for Age-Related Macular Degeneration. In: Ash, J., Grimm, C., Hollyfield, J., Anderson, R., LaVail, M., Bowes Rickman, C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 801. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3209-8_41

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  • DOI: https://doi.org/10.1007/978-1-4614-3209-8_41

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  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-3208-1

  • Online ISBN: 978-1-4614-3209-8

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