Log in

A tissue-engineered approach towards retinal repair: Scaffolds for cell transplantation to the subretinal space

  • Review Article
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

Abstract

Background

Several mechanisms of retina degeneration result in the deterioration of the outer retina and can lead to blindness. Currently, with the exception of anti-angiogenic treatments for wet age-related macular degeneration, there are no treatments that can restore lost vision. There is evidence that photoreceptors and embryonic retinal tissue, transplanted to the subretinal space, can form new synapses with surviving host neurons. However, these transplants have yet to result in a clinical treatment for retinal degeneration.

Methods

This article reviews the current literature on the transplantation of scaffolds with retinal and retinal pigmented epithelial (RPE) cells to the subretinal space. We discuss the types of cells and materials that have been investigated for transplantation to the subretinal space, summarize the current findings, and present opportunities for future research and the next generation of scaffolds for retinal repair.

Results

Challenges to cell transplantation include limited survival upon implantation and the formation of abnormal cell architectures in vivo. Scaffolds have been shown to enhance cell survival and direct cell differentiation and organization in a number of models of retinal degeneration.

Conclusions

The transplantation of cells within a scaffold represents a possible treatment to repair retinal degeneration and restore vision in effected patients. Materials have been developed for the delivery of retinal and RPE cells separately however, the development of a combined tissue-engineered scaffold targeting both cell populations represents a promising direction for retinal repair.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Penn JS, Madan A, Caldwell RB, Bartoli M, Caldwell RW, Hartnett ME (2008) Vascular endothelial growth factor in eye disease. Prog Retin Eye Res 27:331–371

    Article  PubMed  CAS  Google Scholar 

  2. Pieramici DJ, Rabena MD (2008) Anti-VEGF therapy: comparison of current and future agents. Eye 22:1330–1336

    Article  PubMed  CAS  Google Scholar 

  3. Kim SY, Sadda S, Humayun MS, de Juan E Jr, Melia BM, Green WR (2002) Morphometric analysis of the macula in eyes with geographic atrophy due to age-related macular degeneration. Retina 4:464–470

    Article  Google Scholar 

  4. Kim SY, Sadda S, Pearlman J, Humayun MS, de Juan E, Jr MBM, Green WR (2002) Morphometric analysis of the macula in eyes with disciform age-related macular degeneration. Retina 4:471–477

    Article  Google Scholar 

  5. Santos A, Humayun MS, deJuan E, Greenburg RJ, Marsh MJ, Klock IB, Milam AH (1997) Preservation of the inner retina in retinitis pigmentosa—a morphometric analysis. Arch Ophthalmol 115:511–515

    PubMed  CAS  Google Scholar 

  6. Kwan ASL, Wang S, Lund RD (1999) Photoreceptor layer reconstruction in a rodent model of retinal degeneration. Exp Neurol 159:21–33

    Article  PubMed  CAS  Google Scholar 

  7. MacLaren R, Pearson R, MacNeil A, Douglas R, Salt T, Akimoto M, Swaroop A, Sowden J, Ali R (2006) Retinal repair by transplantation of photoreceptor precursors. Nature 444:203–207

    Article  PubMed  CAS  Google Scholar 

  8. Wang S, Girman S , Lu B, Bischoff N, Holmes T, Shearer R, Wright LS, Svendsen CN, Gamm DM, Lund RD (2008) Long-term vision rescue by human neural progenitors in a rat model of photoreceptor degeneration. Investig Ophthalmol Vis Sci 49:3201–3206

    Article  Google Scholar 

  9. Seiler MJ, Thomas B, Chen Z, Wu R, Sadda SR, Aramant RB (2008) Retinal transplants restore visual responses: trans-synaptic tracings from visually responsive sites labels transplant neurons. Eur J NeuroSci 28:208–220

    Article  PubMed  Google Scholar 

  10. Wang S, Lu B, Holmes T, Bischoff N, Lund RD (2008) Morphological and functional rescue in RCS rats after RPE cell line transplantation at a later stage of degeneration. Investig Ophthalmol Vis Sci 49:416–421

    Article  Google Scholar 

  11. Girman SV, Wang S, Lund RD (2003) Cortical visual functions can be preserved by subretinal RPE cell grafting in RCS rats. Vis Res 43:1817–1827

    Article  PubMed  CAS  Google Scholar 

  12. 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 5:53–56

    Article  PubMed  CAS  Google Scholar 

  13. Sagdullaev BT, Aramant RB, Seiler MJ, Woch G, McCall MA (2003) Retinal transplantation-induced recovery of retinotectal visual function in a rodent model of retinitis pigmentosa. Investig Ophthalmol Vis Sci 44:1686–1695

    Article  Google Scholar 

  14. Kwan ASL, Wang S, Lund RD (1999) Photoreceptor layer reconstruction in a rodent model of retinal degeneration. Exp Neurol 159:21–33

    Article  PubMed  CAS  Google Scholar 

  15. Steinberg R (1985) Interactions between the retinal pigment epithelium and the neural retina. Doc Ophthalmol 60:327–346

    Article  PubMed  CAS  Google Scholar 

  16. Tomita M, Lavikb E, Klassen H, Zahir T, Langer R, Young MJ (2005) Biodegradable polymer composite grafts promote the survival and differentiation of retinal progenitor cells. Stem Cells 23:1579–1588

    Article  PubMed  Google Scholar 

  17. Tezel TH, Del Priore LV (1997) Reattachment to a substrate prevents apoptosis of human retinal pigment epithelium. Graefes Arch Clin Exp Ophthalmol 235:41–47

    Article  PubMed  CAS  Google Scholar 

  18. Gouras P, Du J, Kjeldbye H, Yamamoto S, Zack DJ (1994) Long-term photoreceptor transplants in dystrophic and normal mouse retina. Investig Ophthalmol Vis Sci 35:3145–3153

    CAS  Google Scholar 

  19. Young MJ, Ray J, Whiteley SJO, Klassen H, Gage FH (2000) Neuronal differentiation and morphological integration of hippocampal progenitor cells transplanted to the retina of immature mature dystrophic rats. Mol Cell Neurosci 16:197–205

    Article  PubMed  CAS  Google Scholar 

  20. Silverman MS, Hughes SE (1989) Transplantation of photoreceptors to light-damaged retina. Investig Ophthalmol Vis Sci 30:1684–1690

    CAS  Google Scholar 

  21. Ghosh F, Juliusson B, Arner K, Ehinger B (1999) Partial and full-thickness neuroretinal transplants. Exp Eye Res 68:67–74

    Article  PubMed  CAS  Google Scholar 

  22. Aramant RB, Seiler MJ (2004) Progress in retinal sheet transplantation. Prog Retin Eye Res 23:475–494

    Article  PubMed  Google Scholar 

  23. Aramant RB, Seiler MJ, Ball SL (1999) Successful cotransplantation of intact sheets of fetal retinal with retinal pigment epithelium. Investig Ophthalmol Vis Sci 40:1557–1564

    CAS  Google Scholar 

  24. Tansley K (1933) The formation of rosettes in the rat retina. Br J Ophthalmol 17:321–336

    Article  PubMed  CAS  Google Scholar 

  25. Lavik EB, Klassen H, Warfvinge K, Langer R, Young MJ (2005) Fabrication of degradable polymer scaffolds to direct the integration and differentiation of retinal progenitors. Biomaterials 26:3187–3196

    Article  PubMed  CAS  Google Scholar 

  26. Tao S, Young C, Redenti S, Zhang Y, Klassen H, Desai T, Young MJ (2007) Survival, migration and differentiation of retinal progenitor cells transplanted on micro-machined poly(methyl methacrylate) scaffolds to the subretinal space. Royal Soc Chem: Lab Chip 7:695–701

    Article  CAS  Google Scholar 

  27. Lim J, Byun S, Chung S, Park TH, Seo J, Joo C, Chung H, Cho D (2004) Retinal pigment epithelial cell behavior is modulated by alterations in focal cell-substrate contacts. Investig Ophthalmol Vis Sci 45:4210–4216

    Article  Google Scholar 

  28. Vacanti JP, Langer R (1999) Tissue engineering: the design and fabrication of living replacement devices for surgical reconstruction and transplantation. Lancet 354:S32–S34

    Article  Google Scholar 

  29. Langer R (2000) Biomaterials in drug delivery and tissue engineering: one laboratory′s experience. Acc Chem Res 33:94–101

    Article  PubMed  CAS  Google Scholar 

  30. Mano JF, Silva GA, Azevedo HS, Malafaya PB, Sousa RA, Silva SS, Boesel LF, Oliveira JM, Santos TC, Marques AP, Neves NM, Reis RL (2007) Natural origin biodegradable systems in tissue engineering and regenerative medicine: present status and some moving trends. J R Stat Soc: Interface 4:999–1030

    Article  CAS  Google Scholar 

  31. Chan G, Mooney DJ (2008) New materials for tissue engineering: towards greater control over the biological response. Trends Biotech 26:382–392

    Article  CAS  Google Scholar 

  32. Ge Z, ** Z, Cao T (2008) Manufacture of degradable polymeric scaffolds for bone regeneration. Biomed Mater 3:22001

    Article  CAS  Google Scholar 

  33. Khan Y, Yaszemski MJ, Mikos AG, Laurencin CT (2008) Tissue engineering of bone: material and matrix consideration. The Journal of Bone and Joint Surgery, Inc. 90-A:36–42

    Google Scholar 

  34. Nguyen KT, West JL (2002) Photopolymerizable hydrogels for tissue engineering applications. Biomaterials 23:4307–4314

    Article  PubMed  CAS  Google Scholar 

  35. Goldner JS, Bruder JM, Li G, Gazzola D, Hoffman-Kim D (2006) Neurite bridging across micropatterned grooves. Biomaterials 27:460–472

    Article  PubMed  CAS  Google Scholar 

  36. Kobsa S, Saltzman WM (2008) Bioengineering approaches to controlled protein delivery. Pediatr Res 63:513–519

    Article  PubMed  Google Scholar 

  37. Koizumi N, Rigby H, Fullwood NJ, Kawasaki S, Tanioka H, Koizumi K, Kociok N, Joussen AM, Kinoshita S (2007) Comparison of intact and denuded amniotic membrane as a substrate for cell-suspension culture of human limbal epithelial cells. Graefes Arch Clin Exp Ophthalmol 245:123–134

    Article  PubMed  Google Scholar 

  38. Burman S, Tejwani S, Vemuganti GK, Gopinathan U, Sangwan VS (2004) Ophthalmic application of preserved human amniotic membrane: a review of current indications. Cell Tissue Banking 5:161–175

    Article  Google Scholar 

  39. Ohno-Matsui K, Ichinose S, Nakahama K, Yoshida T, Kojima A, Mochizuki M, Morita I (2005) The effects of amniotic membrane on retinal pigment epithelial cell differentiation. Mol Vis 11:1–10

    PubMed  CAS  Google Scholar 

  40. Ohno-Matsui K, Mori K, Ichinose S, Sato T, Wang J, Shimada N, Kojima A, Mochizuki M, Morita I (2006) In vitro and in vivo characterization of iris pigment epithelial cells culture on amniotic membranes. Mol Vis 12:1033–1032

    Google Scholar 

  41. Singh S, Woerly S, McLaughlin BJ (2001) Natural and artificial substrates for retinal pigment epithelial monolayer transplantation. Biomaterials 22:3337–3343

    Article  PubMed  CAS  Google Scholar 

  42. Stanzel BV, Espana EM, Grueterich M, Kawakita T, Parel J, Tseng SCG, Binder S (2005) Amniotic membrane maintains the phenotype of rabbit retinal pigment epithelial cells in culture. Exp Eye Res 80:103–112

    Article  PubMed  CAS  Google Scholar 

  43. Capeans C, Pineiro A, Pardo M, Sueiro-Lopez C, Blanco MJ, Dominguez F, Sanchez-Salorio M (2003) Amniotic membrane as support for human retinal pigment epithelium (RPE) cell growth. Acta Ophthalmol Scand 81:271–277

    Article  PubMed  Google Scholar 

  44. Lee CJ, Huie P, Leng T, Peterman MC, Marmor MF, Blumenkran MS, Bent EF, Fishman HA (2002) Microcontact printing on human tissue for retinal cell transplantation. Arch Ophthalmol 120:1714–1718

    PubMed  Google Scholar 

  45. Lee CL, Fishman HA, Bent SF (2007) Spatial cues for the enhancement of retinal pigment epithelial cell function in potential transplants. Biomaterials 28:2192–2201

    Article  PubMed  CAS  Google Scholar 

  46. Tezel TH, Del Priore LV, Kaplan HJ (2004) Reengineering of aged Bruch′s membrane to enhance retinal pigment epithelium repopulation. Investig Ophthalmol Vis Sci 45:3337–3348

    Article  Google Scholar 

  47. Niknejad H, Peirovi H, Jorjani M, Ahmadiani A, Ghanavi J, Seifalian M (2008) Properties of the amniotic membrane for potential use in tissue engineering. Eur Cells Mater 15:88–99

    CAS  Google Scholar 

  48. Kohane DS, Langer R (2008) Polymeric biomaterials in tissue engineering. Pediatr Res 63:487–489

    Article  PubMed  CAS  Google Scholar 

  49. Colthurst MJ, Williams RL, Hiscott PS, Grierson I (2000) Biomaterials used in the posterior segment of the eye. Biomaterials 21:649–665

    Article  PubMed  CAS  Google Scholar 

  50. Malafaya PB, Silva GA, Reis RL (2007) Natural-origin polymers as carriers and scaffolds for biomolecules and cell delivery in tissue engineering applications. Adv Drug Deliv Rev 59:207–233

    Article  PubMed  CAS  Google Scholar 

  51. Karwatowski WSS, Jeffries TE, Duance VC, Albon J, Bailey AJ, Easty DL (1995) Preparation of Bruch′s membrane and analysis of the age-related changes in the structural collagens. Br J Ophthalmol 79:944–952

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  53. Glowacki J, Mizuno S (2008) Collagen scaffolds for tissue engineering. Biopolymers 89:338–344

    Article  PubMed  CAS  Google Scholar 

  54. Veis A, Cohen J (1960) Reversible transformation of gelatin to the collagen structure. Nature 186:720–721

    Article  PubMed  CAS  Google Scholar 

  55. Del Priore LV, Tezel TH, Kaplan HJ (2004) Survival of allogeneic porcine retinal pigment epithelial sheets after subretinal transplantation. Investig Ophthalmol Vis Sci 45:985–992

    Article  Google Scholar 

  56. Ho TC, Del Priore LV, Kaplan HJ (1996) En bloc transfer of extracellular matrix in vitro. Curr Eye Res 9:991–997

    Article  Google Scholar 

  57. Blomback B (1996) Fibrinogen and fibrin-proteins with complex roles in hemostasis and thrombosis. Thromb Res 83:1–75

    Article  PubMed  CAS  Google Scholar 

  58. Blomback B (1994) Fibrinogen structure, activation, polymerization and fibrin gel structure. Thromb Res 75:327–328

    Article  PubMed  CAS  Google Scholar 

  59. Lavik E, Langer R (2004) Tissue engineering: current state and perspectives. Appl Microbiol Biotechnol 65:108

    Article  CAS  Google Scholar 

  60. Lee CH, Singala A, Lee Y (2001) Biomedical applications of collagen. Int J Pharm 221:1–22

    Google Scholar 

  61. Gunatillake P, Mayadunne R, Adhikari R (2006) Recent developments in biodegradable synthetic polymers. Biotechnol Annu Rev 12:1387–2656

    Google Scholar 

  62. Coombes AGA, Rizzi SC, Williamson M, Barralet JE, Downes S, Wallace WA (2004) Precipitation casting of polycaprolactone for applications in tissue engineering and drug delivery. Biomaterials 25:315–325

    Article  PubMed  CAS  Google Scholar 

  63. Wang Y, Ameer GA, Sheppard BJ, Langer R (2002) A tough biodegradable elastomer. Nat Biotechnol 20:602–606

    Article  PubMed  CAS  Google Scholar 

  64. Neeley WL, Redenti S, Klassen H, Tao S, Desai T, Young MJ, Langer R (2008) A microfabricated scaffold for retinal progenitor cell grafting. Biomaterials 29:418–426

    Article  PubMed  CAS  Google Scholar 

  65. Page WJ, Manchak J, Rudy B (1992) Formation of poly(hydroxybutyrate-co-hydroxyvalerate) by Azotobacter vinelandii UWD. Appl Environ Microbiol 58:2866–2873

    PubMed  CAS  Google Scholar 

  66. Tezcaner A, Bugra K, Hasirci V (2003) Retinal pigmented epithelium cell culture on surface modified poly(hydroxybutyrate-co-hydroxyvalerate) thin films. Biomaterials 24:4573–4583

    Article  PubMed  CAS  Google Scholar 

  67. Eberli D, Freitas L, Atala A, Yoo JJ (2009) Composite scaffolds for the engineering of hollow organs and tissues. Methods 47:109–115

    Article  PubMed  CAS  Google Scholar 

  68. Giordano GG, Thomas RC, Ishaug SL, Mikos AG, Cumber S, Garcia CA, Lahiri-Munir D (1997) Retinal pigment epithelium cells cultured on synthetic biodegradable polymers. J Biomed Mater Res 34:87–93

    Article  PubMed  CAS  Google Scholar 

  69. Thomson RC, Giordano GG, Collier JH, Ishaug SL, Mikos AG, Lahiri-Munir D, Garcia CA (1996) Manufacture and characterization of poly(a-hydroxy ester) thin films as temporary substrates for retinal pigment epithelium cells. Biomaterials 17:321–327

    Article  PubMed  CAS  Google Scholar 

  70. Mikos AG, Lyman LE, Freed LE, Langer R (1994) Wetting of poly(L-lactic acid) and poly(DL-lactic-co-glycolic acid) foams for tissue culture. Biomaterials 1:55–58

    Article  Google Scholar 

  71. Mikos AG, Sarakinos G, Lyman MD, Ingber DE, Vacanti JP, Langer R (1993) Prevascularization of porous biodegradable polymers. Biotechnol Bioeng 42:716–723

    Google Scholar 

  72. Schugens C, Maquet V, Grandfils Ch, Jerome R, Teyssie Ph (1996) Polylactide macroporous biodegradable implants for cell transplantation. II. Preparation of polylactide foams by liquid–liquid phase separation. J Biomed Materi Res 30:449–461

    Article  CAS  Google Scholar 

  73. Schugens C, Maquet V, Grandfils C, Jerome R, Teyssie P (1996) Biodegradable and macroporous polylactide implants for cell transplantation: 1. Preparation of macroporous polylactide supports by solid–liquid phase separation. Polymer 37:1027–1038

    Article  CAS  Google Scholar 

  74. Truskett VN, Watts MPC (2006) Trends in imprint lithography for biological applications. Trends Biotechnol 24:312–317

    Article  PubMed  CAS  Google Scholar 

  75. Borenstein JT, Weinberg EJ, Orrick BK, Sundback C, Kaazempur-Mofrad MR, Vacanti JP (2007) Microfabrication of three-dimensional engineered scaffolds. Tissue Eng 13:1837–1844

    Article  PubMed  CAS  Google Scholar 

  76. Andersson H, van den Berg A (2004) Microfabrication and microfluidics for tissue engineering; state of the art and future opportunities. Lab Chip 4:98–103

    Article  PubMed  CAS  Google Scholar 

  77. Hill JZ, Peppas NA (2005) Microfabricated drug delivery devices. Int J Pharm 306:15–23

    Article  CAS  Google Scholar 

  78. Tao SL, Desai TA (2003) Microfabricated drug delivery systems: from particles to pores. Adv Drug Deliv Rev 55:315–328

    Article  PubMed  CAS  Google Scholar 

  79. Tao SL, Desai TA (2005) Micromachined devices: the impact of controlled geometry from cell-targeting to bioavailability. J Control Release 109:127–138

    Article  PubMed  CAS  Google Scholar 

  80. Falconnett D, Csucs G, Grandin HM, Textor M (2006) Surface engineering approaches to micropattern surfaces for cell-based assays. Biomaterials 27:3044–3063

    Article  CAS  Google Scholar 

  81. Tezcaner A, Hicks D (2007) In vitro characterization of micropatterned PLGA-PHBV8 blend films as temporary scaffolds for photoreceptor cells. J Biomed Mater Res Part A 170-181

  82. Weibel DB, Garstecki,P, Whitesides GM (2005) Combining microscience and neurobiology. Curr Opin Neurobiol 15:560–567

    Article  PubMed  CAS  Google Scholar 

  83. Gouras P, Du J, Gelanze M, Lopez R, Kwun R, Kjeldbye H, Krebs W (1991) Survival and synapse formation of transplanted rat rods. J Neural Transpl Plast 2:91–100

    Article  CAS  Google Scholar 

  84. Schuschereba ST, Silverman MS (1992) Retinal cell and photoreceptor transplantation between adult New Zealand Red Rabbit retinas. Exp Neurobiol 115:95–99

    Article  CAS  Google Scholar 

  85. Silverman MS, Hughes SE, Valentino TL, Liu Y (1992) Photoreceptor transplantation: anatomic, electophysiologic, and behavioral evidence for the functional reconstruction of retinas lacking photoreceptors. Exp Neurol 115:87–94

    Article  PubMed  CAS  Google Scholar 

  86. Berson EL, Jakobiec FA (1999) Neural retinal cell transplantation: ideal versus reality. Ophthalmology 106:445–446

    Article  PubMed  CAS  Google Scholar 

  87. Schraermeyer U, Thumann G, Luther T, Kociok N, Armhold S, Kruttwig K, Andressen C, Addics K, Bartz-Schmidt KU (2001) Subretinally transplanted embryonic stem cells rescue photoreceptor cells from degeneration in the RCS rats. Cell Transplant 10:673–680

    PubMed  CAS  Google Scholar 

  88. Haruta M, Takahashi M (2005) Embryonic stem cells: potential source for ocular repair. Sem Ophthalmol 20:17–23

    Article  Google Scholar 

  89. Arnold S, Klein H, Semkova I, Addicks K, Schraermeyer U (2004) Neurally selected embryonic stem cells induce tumor formation after long-term survival following engraftment into the subretinal space. Investig Ophthalmol Vis Sci 45:4251–4255

    Article  Google Scholar 

  90. 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 4:73–79

    Article  PubMed  CAS  Google Scholar 

  91. Zhao X, Lin J, Ahmad I (2002) Differentiation of embryonic stem cells into retinal neurons. Biochem Biophys Res Commun 297:177–184

    Article  PubMed  CAS  Google Scholar 

  92. 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. Investig Ophthalmol Vis Sci 45:1020–1025

    Article  Google Scholar 

  93. Vugler A, Lawrence J, Walsh J, Carr A, Gias C, Semo M, Ahmado A, da Cruz L, Andrews P, Coffey P (2007) Embryonic stem cells and retinal repair. Mech Dev 124:807–829

    Article  PubMed  CAS  Google Scholar 

  94. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Steward R, Slukvin II, Thomson JA (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917–1920

    Article  PubMed  CAS  Google Scholar 

  95. 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 27:2427–2434

    Article  PubMed  CAS  Google Scholar 

  96. Li W, Zhou H, Abujarour R, Zhu S, Joo JY, Lin T, Hao E, Scholer HR, Hayek A, Ding S (2009) Generation of human-induced pluripotent stem cells in the absence of exogenous SOX2. Stem Cells Epub ahead of print

  97. Gage FH, Coates PW, Palmer TD, Kuhn HG, Fischer LJ, Suhonen JO, Peterson DA, Suhr ST, Ray J (1995) Survival and differentiation of adult neuronal progenitor cells transplanted to the adult brain. PNAS 92:11879–11883

    Article  PubMed  CAS  Google Scholar 

  98. Gage FH (2000) Mammalian neural stem cells. Science 287:1433–1438

    Article  PubMed  CAS  Google Scholar 

  99. Takahashi M, Palmer TD, Takahashi J, Gage FH (1998) Widespread integration and survival of adult-derived neural progenitor cells in the develo** optic retina. Mol Cell Neurosci 12:340–348

    Article  PubMed  CAS  Google Scholar 

  100. Mizumoto H, Mizumoto K, Shatos MA, Klassen H, Young MJ (2003) Retinal transplantation of neural progenitor cells derived from the brain of GFP transgenic mice. Vis Res 43:1699–1708

    Article  PubMed  Google Scholar 

  101. Tropepe V, Coles BLK, Chiasson BJ, Horsford DJ, Elia AJ, McInnes RR, van der Kooy D (2000) Retinal stem cells in the adult mammalian eye. Science 287:2032–2036

    Article  PubMed  CAS  Google Scholar 

  102. Shatos M, Mizumoto K, Mizumoto H, Kurimoto Y, Klassen H, Young M (2001) Multipotent stem cells from the brain and retina of green mice. Regenerative Med 2:13–15

    Article  CAS  Google Scholar 

  103. Chacko DM, Rogers JA, Turner JE, Ahmad I (2000) Survival and differentiation of cultured retinal progenitors transplanted in the subretinal space of the rat. Biochem Biophys Res Commun 268:842–846

    Article  PubMed  CAS  Google Scholar 

  104. Djojosubroto MW, Arsenijevic Y (2007) Retinal stem cells: promising candidates for retina transplantation. Cell Tissue Res 331:347–357

    Google Scholar 

  105. MacLaren RE, Pearson RA (2007) Stem cell therapy and the retina. Eye 21:1352–1359

    Article  PubMed  CAS  Google Scholar 

  106. Binder S, Stanzel BV, Krebs I, Glittenber C (2007) Transplantation of the RPE in AMD. Prog Retin Eye Res 26:516–554

    Article  PubMed  Google Scholar 

  107. da Cruz L, Chen FK, Ahmado A, Greenwood J, Coffey P (2007) RPE transplantation and its role in retinal disease. Prog Retin Eye Res 26:598–635

    Article  PubMed  CAS  Google Scholar 

  108. Abe T, Yoshida M, Yoshioka Y, Wakusawa R, Tokita-Ishikawa Y, Seto H, Tamai M, Nishiad K (2007) Iris pigment epithelial cell transplantation for degenerative retinal diseases. Prog Retin Eye Res 26:302–321

    Article  PubMed  CAS  Google Scholar 

  109. Gouras P, Flood MT, Kjedbye H, Bilek MK, Eggers H (1985) Transplantation of cultured retinal epithelium to Bruch′s membrane of the owl monkey′s eye. Curr Eye Res 3:253–265

    Article  Google Scholar 

  110. Li LX, Turner JE (1988) Transplantation of retinal pigment epithelial cells to immature and adult rat hosts: short- and long-term survival characteristics. Exp Eye Res 47:771–785

    Article  PubMed  CAS  Google Scholar 

  111. Li LX, Turner JE (1991) Optimal conditions for long-term photoreceptors cell rescue in RCS rats: the necessity for healthy RPE transplants. Exp Eye Res 52:669–679

    Article  PubMed  CAS  Google Scholar 

  112. Lopez R, Gouras P, Kjeldbye H, Sullivan B, Reppucci V, Brittis M, Waper F, Goluboff E (1989) Transplanted retinal pigmented epithelium modifies the retinal degeneration in the RCS rat. Investig Ophthalmol Vis Sci 3:586–588

    Google Scholar 

  113. Sheng Y, Gouras P, Cao H, Berglin L, Kjeldbye H, Lopez R, Rosskothen H (1995) Patch transplants of human fetal retinal pigment epithelium in rabbit and monkey retina. Investig Ophthalmol Vis Sci 36:381–390

    CAS  Google Scholar 

  114. Seiler MJ, Aramant RB, Bergstrom A (1995) Co-transplantation of embryonic retina and retinal pigment epithelial cells to rabbit retina. Curr Eye Res 3:199–207

    Article  Google Scholar 

  115. Binder S, Stolba U, Krebs I, Kellber L, Jahn C, Feichtinger H, Povelka M, Frohner U, Kruger A, Hilgers R, Krugluger W (2002) Transplantation of autologous retinal pigment epithelium in eyes with foveal neovascularization resulting from age-related macular degeneration: a pilot study. Am J Ophthalmol 133:215–225

    Article  PubMed  Google Scholar 

  116. van Meurs JC, ter Averst E, Hofland LJ, van Hagen PM, Mooy CM, Baarsma GS, Kuijpers RP, Boks T, Stalmans P (2004) Autologous peripheral retinal pigment epithelium translocation in patients with subfoveal neovascular membranes. Br J Ophthalmol 88:110–113

    Article  PubMed  Google Scholar 

  117. Rezai KA, Lappas A, Kohen L, Wiedemann P, Heimann K (1997) Comparison of tight junction permeability for albumin in iris pigment epithelium and retinal pigment epithelium in vitro. Graefes Arch Clin Exp Ophthalmol 235:48–55

    Article  PubMed  CAS  Google Scholar 

  118. Sakuragi M, Tomita H, Abe T, Tamai M (2001) Changes of phagocytic capacity in basic fibroblast growth factor-transfected iris pigment epithelial cells in rats. Curr Eye Res 23:185–191

    Article  PubMed  CAS  Google Scholar 

  119. Schraermeyer U, Enzmann V, Kohen L, Addicks K, Wiedemann P, Heimann K (1997) Porcine iris pigment epithelial cells can take up retinal outer segments. Exp Eye Res 65:277–287

    Article  PubMed  CAS  Google Scholar 

  120. Aramant RB, Seiler MJ (2002) Retinal transplantation—advantages of intact fetal sheets. Prog Retin Eye Res 21:57–73

    Article  PubMed  Google Scholar 

  121. Bergstrom A, Ehinger B, Wilke K, Zucker CL, Adolph AR, Aramant R, Seiler M (1992) Transplantation of embryonic retina to the subretinal space in rabbits. Exp Eye Res 55:29–37

    Article  PubMed  CAS  Google Scholar 

  122. Ghosh F, Ehinger B (2000) Full-thickness retinal transplants: a review. Opthalmologica 214:54–69

    Article  CAS  Google Scholar 

  123. Aramant RB, Seiler MJ (2004) Progress in retinal sheet transplantation. Prog Retin Eye Res 23:475–494

    Article  PubMed  Google Scholar 

  124. Radtke ND, Aramant RB, Petry HM, Green PT, Pidwell DJ, Seiler MJ (2008) Vision improvement in retinal degeneration patients by implantation of retina together with retinal pigment epithelium. Am J Ophthalmol 146:172–182

    Google Scholar 

  125. Doi K, Kong J, Hargitai J, Goff SP, PG (2004) Transient immunosuppression stops rejection of virus-transduced enhanced green fluorescent protein in rabbit retina 78:11327–11333

  126. Lai C, Gouras P, Doi K, Tsang SH (2000) Local immunosuppression prolongs survival of RPE xenografts labeled by retroviral gene transfer. Investig Ophthalmol Vis Sci 41:3134–3141

    Google Scholar 

  127. Ng TF, Klassen H, Hori J, Young MJ (2007) Retinal transplantation. Immune Response and the Eye 92:300–316

    Google Scholar 

  128. Teixeira AI, Duckworth JK, Hermanson O (2007) Getting the right stuff: controlling neural stem cell state and fate in vivo and in vitro with biomaterials. Cell Res 17:56–61

    Article  PubMed  CAS  Google Scholar 

  129. Huang JC, Ishida M, Hersh P, Sugino IK, Zarbin MA (1998) Preparation and transplantation of photoreceptor sheets. Curr Eye Res 17:573–585

    Article  PubMed  CAS  Google Scholar 

  130. Hsiue G, Lai JY, Lin PK (2002) Absorbable sandwich-like membrane for retinal-sheet transplantation. J Biomed Materi Res 61:19–25

    Article  CAS  Google Scholar 

  131. Khodair MA, Zarbin MA, Townes-Anderson E (2003) Synaptic plasticity in mammalian photoreceptors prepared as sheets for retinal transplantation. Investig Ophthalmol Vis Sci 44:4976–4988

    Article  Google Scholar 

  132. Seiler MJ, Thomas BB, Chen Z, Arai S, Chadalavada S, Mahoney MJ, Sadda SR, Aramant RB (2008) BDNF-treated retinal progenitor sheets transplanted to degenerate rats: improved restoration of visual function. Exp Eye Res 86:92–104

    Article  PubMed  CAS  Google Scholar 

  133. Chaum E (2003) Retinal neuroprotection by growth factors: a mechanistic perspective. J Cell Biochem 88:57–75

    Article  PubMed  CAS  Google Scholar 

  134. Bhatt NS, Newsome DA, Fenech T, Hessburg TP, Diamond JG, Miceli MV, Kratz KE, Oliver PD (1994) Experimental transplantation of human retinal pigment epithelial cells on collagen substrates. Am J Ophthalmol 117:214–221

    PubMed  CAS  Google Scholar 

  135. Lu JT, Lee CJ, Bent SF, Fischmann HA, Sabelman EE (2007) Thin collagen film scaffolds for retinal epithelial cell culture. Biomaterials 28:1486–1494

    Article  PubMed  CAS  Google Scholar 

  136. Thumann G, Hueber A, Dinslage S, Schaeger F, Yasukawa T, Kirchhof B, Yafai Y, Eichler W, Bringmann A, Wiedemann P (2006) Characteristics of iris and retinal pigment epithelial cells cultures on collagen type I membranes. Curr Eye Res 31:241–249

    Article  PubMed  CAS  Google Scholar 

  137. Imai H, Honda S, Kondo N, Ishibashi K, Tsukahara Y, Negi A (2007) The upregulation of angiogenic gene expression in cultured retinal pigment epithelial cells grown on type I collagen. Curr Eye Res 32:903–910

    Article  PubMed  CAS  Google Scholar 

  138. Farrokh-Siar L, Rezai KA, Patel SC, Ernest JT (1999) Cryoprecipitate: an autologous substrate for human fetal retinal pigment epithelium. Curr Eye Res 19:89–94

    Article  PubMed  CAS  Google Scholar 

  139. Ho T, Del Priore LV (1997) Reattachment of cultured human retinal pigment epithelium to extracellular matrix and human Bruch′s membrane. Investig Ophthalmol Vis Sci 38:1110–1118

    CAS  Google Scholar 

  140. Oganesian A, Gabrielian K, Ernest JT, Patel SC (1999) A new model of retinal pigment epithelium transplantation with microspheres. Arch Ophthalmol 117:1192–1200

    PubMed  CAS  Google Scholar 

  141. Thumann G, Schraermeyer U, Bartz-Schmidt KU, Heimann K (1997) Descemet′s membrane as membranous support in RPE/IPE. Curr Eye Res 12:1236–1238

    Article  Google Scholar 

  142. Beutel J, Greulich L, Luke M, Ziemssen F, Szurman P, Bartz-Schmidt K, Grisanti S (2007) Inner limiting membrane as membranous support in RPE sheet-transplantation. Graefes Arch Clin Exp Ophthalmol 245:1469–1473

    Article  PubMed  Google Scholar 

  143. Hartmann U, Sistani F, Steinhorst UH (1999) Human and porcine anterior lens capsule as support for growing and grafting retinal pigment epithelium and iris pigment epithelium. Graefes Arch Clin Exp Ophthalmol 237:940–945

    Article  PubMed  CAS  Google Scholar 

  144. Singhal S, Vemuganti GK (2005) Primary adult human retinal pigment epithelial cell cultures on human amniotic membranes. Indian J Ophthalmol 53:109–113

    Article  PubMed  Google Scholar 

  145. Nicolini J, Kiilgaard JF, Wiencke AK, Heegaard S, Scherfig E, Prause JU, la Cour M (2000) The anterior lens capsule used as support material in RPE cell-transplantation. Acta Ophthalmol Scand 78:527–531

    Article  PubMed  CAS  Google Scholar 

  146. Hadlock T, Singh S, Vacanti JP, McLaughlin BJ (1999) Ocular cell monolayers cultured on biodegradable substrates. Tissue Eng 5:187–196

    Article  PubMed  CAS  Google Scholar 

  147. Lu L, Garcia CA, Mikos GA (1998) Retinal pigment epithelium cell culture on thin biodegradable poly(DL-lactic-co-glycolic acid) films. J Biomater Sci Polym Ed 9:1187–1205

    Article  PubMed  CAS  Google Scholar 

  148. Lu LC, Yaszemski MJ, Mikos AG (2001) Retinal pigment epithelium engineering using synthetic biodegradable polymers. Biomaterials 22:3345–3355

    Article  PubMed  CAS  Google Scholar 

  149. Singh S, Woerly S, McLaughlin B (2001) Natural and artificial substrates for retinal pigment epithelial monolayer transplantation. Biomaterials 22:3337–3343

    Article  PubMed  CAS  Google Scholar 

  150. von Recum H, Kikuchi A, Minako O, Yahuhisa S, Teruo O, Kim SW (1998) Retinal pigmented epithelium cultures on thermally responsive polymer porous substrates. J Biomater Sci Polym Ed 9:1241–1253

    Article  Google Scholar 

  151. Qui G, Seiler M, Arai S, Aramant R, Sadda S (2004) Alternative culture conditions for isolation and expansion of retinal progenitor cells. Curr Eye Res 28:327–336

    Google Scholar 

  152. Hynes SR, Rauch MF, Bertram JP, Lavik EB (2008) A library of tunable poly(ethylene glycol)/poly(L-lysine) hydrogels to investigate the material cues that influence neural stem cell differentiation. J Biomed Mater Res Part A 89:499–509

    Google Scholar 

  153. Madihally SV, Matthew HWT (1999) Porous chitosan scaffolds for tissue engineering. Biomaterials 20:1133–1142

    Article  PubMed  CAS  Google Scholar 

  154. Lei M, Gu Y, Baldi A, Siegel RA, Ziaie B (2004) Soft mold-dry etch: a novel hydrogel patterning technique for biomedical applications. Procceedings of the 26th Annual International Conference of the IEEE EMBS 1983–1986

  155. Ford MC, Bertram JP, Hynes SR, Michaud M, Li Q, Young M, Segal SS, Madri JA, Lavik EB (2006) A macroporous hydrogel for the coculture of neural progenitor and endothelial cells to form functional vascular networks in vivo. Proc Natl Acad Sci USA 103:2512–2517

    Article  PubMed  CAS  Google Scholar 

  156. Guenther E, Troger B, Schlosshauer B, Zrenner E (1999) Long-term survival of retinal cell cultures on retinal implant materials. Vision Res. 39:3988–3994

    Article  PubMed  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  158. Wu H, Li X, Dong J, Pei W, Chen H (2007) Effects of subretinal implant materials on viability, apoptosis and barrier function of cultured RPE cells. Graefes Arch Clin Exp Ophthalmol 245:135–142

    Article  PubMed  Google Scholar 

  159. Beutel J, Greulich L, Luke M, Ziemssen F, Szurman P, Bartz-Schmidt K, Grisanti S (2007) Inner limiting membrane as membranous support in RPE shee-transplantation. Graefes Arch Clin Exp Ophthalmol 245:1469–1473

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Erin B. Lavik.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hynes, S.R., Lavik, E.B. A tissue-engineered approach towards retinal repair: Scaffolds for cell transplantation to the subretinal space. Graefes Arch Clin Exp Ophthalmol 248, 763–778 (2010). https://doi.org/10.1007/s00417-009-1263-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00417-009-1263-7

Keywords

Navigation