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Differentiation of Human Pluripotent Stem Cells into Retinal Cells

  • Masha Idelson
  • Benjamin Reubinoff
Chapter
Part of the Stem Cells and Cancer Stem Cells book series (STEM, volume 6)

Abstract

Retinal and macular degeneration disorders are characterized by a progressive loss of photoreceptors, which causes visual impairment and blindness. In some cases, the visual loss is caused by dysfunction, degeneration and loss of underlying retinal pigment epithelial (RPE) cells and the subsequent death of photoreceptors. The grim reality is that there is no successful treatment for most of these blindness disorders. Cell therapy aimed at replenishing the degenerating cells is considered a potential therapeutic approach that may delay, halt or perhaps even reverse degeneration, as well as improve retinal function and prevent blindness in the aforementioned conditions. Human embryonic stem cells (hESC) and induced pluripotent stem cells (iPSCs) may serve as an unlimited donor source of photoreceptors and RPE cells for transplantation into degenerating retinas and for retinal disease modeling.

Keywords

Retinal Pigment Epithelium Retinal Pigment Epithelium Cell Retinitis Pigmentosa Retinal Degeneration Neural Retina 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Banin E, Obolensky A, Idelson M, Hemo I, Reinhardtz E, Pikarsky E, Ben-Hur T, Reubinoff B (2006) Retinal incorporation and differentiation of neural precursors derived from human embryonic stem cells. Stem Cells 24:246–257PubMedCrossRefGoogle Scholar
  2. Binder S, Krebs I, Hilgers RD, Abri A, Stolba U, Assadoulina A, Kellner L, Stanzel BV, Jahn C, Feichtinger H (2004) Outcome of transplantation of autologous retinal pigment epithelium in age-related macular degeneration: a prospective trial. Invest Ophthalmol Vis Sci 45:4151–4160PubMedCrossRefGoogle Scholar
  3. Buchholz DE, Hikita ST, Rowland TJ, Friedrich AM, Hinman CR, Johnson LV, Clegg DO (2009) Derivation of functional retinal pigmented epithelium from induced pluripotent stem cells. Stem Cells 27:2427–2434PubMedCrossRefGoogle Scholar
  4. Coffey PJ, Girman S, Wang SM, Hetherington L, Keegan DJ, Adamson P, Greenwood J, Lund RD (2002) Long-term preservation of cortically dependent visual function in RCS rats by transplantation. Nat Neurosci 5:53–56PubMedCrossRefGoogle Scholar
  5. Cook HL, Patel PJ, Tufail A (2008) Age-related macular degeneration: diagnosis and management. Br Med Bull 85:127–149PubMedCrossRefGoogle Scholar
  6. D’Cruz PM, Yasumura D, Weir J, Matthes MT, Abderrahim H, LaVail MM, Vollrath D (2000) Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat. Hum Mol Genet 9:645–651PubMedCrossRefGoogle Scholar
  7. da Cruz L, Chen FK, Ahmado A, Greenwood J, Coffey P (2007) RPE transplantation and its role in retinal disease. Prog Retin Eye Res 26:598–635PubMedCrossRefGoogle Scholar
  8. Durnaoglu S, Genc S, Genc K (2011) Patient-specific pluripotent stem cells in neurological diseases. Stem Cells Int 2011:212487. doi: 10.4061/2011/212487 PubMedGoogle Scholar
  9. Eiraku M, Takata N, Ishibashi H, Kawada M, Sakakura E, Okuda S, Sekiguchi K, Adachi T, Sasai Y (2011) Self-organizing optic-cup morphogenesis in three-dimensional culture. Nature 472:51–56PubMedCrossRefGoogle Scholar
  10. Fuhrmann S, Levine EM, Reh TA (2000) Extraocular mesenchyme patterns the optic vesicle during early eye development in the embryonic chick. Development 127:4599–4609PubMedGoogle Scholar
  11. Ghosh F, Bruun A, Ehinger B (1999) Graft-host connections in long-term full-thickness embryonic rabbit retinal transplants. Invest Ophthalmol Vis Sci 40:126–132PubMedGoogle Scholar
  12. Harada T, Harada C, Parada LF (2007) Molecular regulation of visual system development: more than meets the eye. Genes Dev 21:367–378PubMedCrossRefGoogle Scholar
  13. Hartong DT, Berson EL, Dryja TP (2006) Retinitis pigmentosa. Lancet 368:1795–1809PubMedCrossRefGoogle Scholar
  14. Haruta M, Sasai Y, Kawasaki H, Amemiya K, Ooto S, Kitada M, Suemori H, Nakatsuji N, Ide C, Honda Y, Takahashi M (2004) In vitro and in vivo characterization of pigment epithelial cells differentiated from primate embryonic stem cells. Invest Ophthalmol Vis Sci 45:1020–1025PubMedCrossRefGoogle Scholar
  15. Idelson M, Alper R, Obolensky A, Ben-Shushan E, Hemo I, Yachimovich-Cohen N, Khaner H, Smith Y, Wiser O, Gropp M, Cohen MA, Even-Ram S, Berman-Zaken Y, Matzrafi L, Rechavi G, Banin E, Reubinoff B (2009) Directed differentiation of human embryonic stem cells into functional retinal pigment epithelium cells. Cell Stem Cell 5:396–408PubMedCrossRefGoogle Scholar
  16. Jin ZB, Okamoto S, Osakada F, Homma K, Assawachananont J, Hirami Y, Iwata T, Takahashi M (2011) Modeling retinal degeneration using patient-specific induced pluripotent stem cells. PLoS One 6(2):e17084. doi: 10.1371/journal.pone.0017084 PubMedCrossRefGoogle Scholar
  17. Kaneko H, Dridi S, Tarallo V, Gelfand BD, Fowler BJ, Cho WG, Kleinman ME, Ponicsan SL, Hauswirth WW, Chiodo VA, Karikó K, Yoo JW, Lee DK, Hadziahmetovic M, Song Y, Misra S, Chaudhuri G, Buaas FW, Braun RE, Hinton DR, Zhang Q, Grossniklaus HE, Provis JM, Madigan MC, Milam AH, Justice NL, Albuquerque RJ, Blandford AD, Bogdanovich S, Hirano Y, Witta J, Fuchs E, Littman DR, Ambati BK, Rudin CM, Chong MM, Provost P, Kugel JF, Goodrich JA, Dunaief JL, Baffi JZ, Ambati J (2011) DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration. Nature 471:325–330PubMedCrossRefGoogle Scholar
  18. Kawasaki H, Suemori H, Mizuseki K, Watanabe K, Urano F, Ichinose H, Haruta M, Takahashi M, Yoshikawa K, Nishikawa S, Nakatsuji N, Sasai Y (2002) Generation of dopaminergic neurons and pigmented epithelia from primate ES cells by stromal cell-derived inducing activity. Proc Natl Acad Sci USA 99:1580–1585PubMedCrossRefGoogle Scholar
  19. 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 6:217–245PubMedGoogle Scholar
  20. Lamba DA, Reh TA (2011) Microarray characterization of human embryonic stem cell-derived retinal cultures. Invest Ophthalmol Vis Sci 52:4897–4906PubMedCrossRefGoogle Scholar
  21. Lamba DA, Karl MO, Ware CB, Reh TA (2006) Efficient generation of retinal progenitor cells from human embryonic stem cells. Proc Natl Acad Sci USA 103:12769–12774PubMedCrossRefGoogle Scholar
  22. Lamba DA, Gust J, Reh TA (2009) Transplantation of human embryonic stem cell-derived photoreceptors restores some visual function in Crx-deficient mice. Cell Stem Cell 4:73–79PubMedCrossRefGoogle Scholar
  23. Li LX, Turner JE (1988) Inherited retinal dystrophy in the RCS rat: prevention of photoreceptor degeneration by pigment epithelial cell transplantation. Exp Eye Res 47:911–917PubMedCrossRefGoogle Scholar
  24. Lu B, Malcuit C, Wang S, Girman S, Francis P, Lemieux L, Lanza R, Lund R (2009) Long-term safety and function of RPE from human embryonic stem cells in preclinical models of macular degeneration. Stem Cells 27:2126–2135PubMedCrossRefGoogle Scholar
  25. Lund RD, Kwan AS, Keegan DJ, Sauvé Y, Coffey PJ, Lawrence JM (2001) Cell transplantation as a treatment for retinal disease. Prog Retin Eye Res 20:415–449PubMedCrossRefGoogle Scholar
  26. Lund RD, Wang S, Klimanskaya I, Holmes T, Ramos-Kelsey R, Lu B, Girman S, Bischoff N, Sauvé Y, Lanza R (2006) Human embryonic stem cell-derived cells rescue visual function in dystrophic RCS rats. Cloning Stem Cells 8:189–199PubMedCrossRefGoogle Scholar
  27. Martínez-Morales JR, Rodrigo I, Bovolenta P (2004) Eye development: a view from the retina pigmented epithelium. Bioessays 26:766–777PubMedCrossRefGoogle Scholar
  28. Meyer JS, Shearer RL, Capowski EE, Wright LS, Wallace KA, McMillan EL, Zhang SC, Gamm DM (2009) Modeling early retinal development with human embryonic and induced pluripotent stem cells. Proc Natl Acad Sci USA 106:16698–16703PubMedCrossRefGoogle Scholar
  29. Meyer JS, Howden SE, Wallace KA, Verhoeven AD, Wright LS, Capowski EE, Pinilla I, Martin JM, Tian S, Stewart R, Pattnaik B, Thomson JA, Gamm DM (2011) Optic vesicle-like structures derived from human pluripotent stem cells facilitate a customized approach to retinal disease treatment. Stem Cells 29:1206–1218PubMedCrossRefGoogle Scholar
  30. Miyoshi N, Ishii H, Nagano H, Haraguchi N, Dewi DL, Kano Y, Nishikawa S, Tanemura M, Mimori K, Tanaka F, Saito T, Nishimura J, Takemasa I, Mizushima T, Ikeda M, Yamamoto H, Sekimoto M, Doki Y, Mori M (2011) Reprogramming of mouse and human cells to pluripotency using mature microRNAs. Cell Stem Cell 8:633–638PubMedCrossRefGoogle Scholar
  31. Osakada F, Ikeda H, Mandai M, Wataya T, Watanabe K, Yoshimura N, Akaike A, Sasai Y, Takahashi M (2008) Toward the generation of rod and cone photoreceptors from mouse, monkey and human embryonic stem cells. Nat Biotechnol 26:215–224PubMedCrossRefGoogle Scholar
  32. Osakada F, Jin ZB, Hirami Y, Ikeda H, Danjyo T, Watanabe K, Sasai Y, Takahashi M (2009) In vitro differentiation of retinal cells from human pluripotent stem cells by small-molecule induction. J Cell Sci 122:3169–3179PubMedCrossRefGoogle Scholar
  33. Reubinoff BE, Pera MF, Fong CY, Trounson A, Bongso A (2000) Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro. Nat Biotechnol 18:399–404PubMedCrossRefGoogle Scholar
  34. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872PubMedCrossRefGoogle Scholar
  35. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM (1998) Embryonic stem cell lines derived from human blastocysts. Science 282:1145–1147PubMedCrossRefGoogle Scholar
  36. Thumann G, Viethen A, Gaebler A, Walter P, Kaempf S, Johnen S, Salz AK (2009) The in vitro and in vivo behavior of retinal pigment epithelial cells cultured on ultrathin collagen membranes. Biomaterials 30:287–294PubMedCrossRefGoogle Scholar
  37. Turner JE, Blair JR (1986) Newborn rat retinal cells transplanted into a retinal lesion site in adult host eyes. Brain Res 391:91–104PubMedGoogle Scholar
  38. Vugler A, Carr AJ, Lawrence J, Chen LL, Burrell K, Wright A, Lundh P, Semo M, Ahmado A, Gias C, da Cruz L, Moore H, Andrews P, Walsh J, Coffey P (2008) Elucidating the phenomenon of HESC-derived RPE: anatomy of cell genesis, expansion and retinal transplantation. Exp Neurol 214:347–361PubMedCrossRefGoogle Scholar
  39. Walia S, Fishman GA (2009) Natural history of phenotypic changes in Stargardt macular dystrophy. Ophthalmic Genet 30:63–68PubMedCrossRefGoogle Scholar
  40. Weisz JM, Humayun MS, De Juan E Jr, Del Cerro M, Sunness JS, Dagnelie G, Soylu M, Rizzo L, Nussenblatt RB (1999) Allogenic fetal retinal pigment epithelial cell transplant in a patient with geographic atrophy. Retina 19:540–545PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  1. 1.The Hadassah Human Embryonic Stem Cell Research Center, The Goldyne Savad Institute of Gene Therapy & The Department of Obstetrics and GynecologyHadassah University Medical CenterJerusalemIsrael

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