Progresses of cell-based therapy and tissue engineering in the treatment of age-related macular degeneration_Chinese Journal of Ocular Fundus Diseases

Authors：

ShaoBing , ChenDi ,  MinHanyi

Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100730, China;

Corresponding author：

MinHanyi, Email: wredge@sohu.com

Keywords：

Macular degeneration/therapy; Tissue therapy; Tissue engineering; Review

DOI：

10.3760/cma.j.issn.1005-1015.2016.01.025

Video：

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Age-related macular degeneration (AMD) has become one of the leading causes of irreversible blindness worldwide. With the advancement of stem cell technology, tissue engineering and biomaterials, cell-based therapy has been inspiring for many degenerative diseases. For its unique advantages, AMD has become one of the most promising fields for cell-based therapy, which involve retinal pigment epithelium (RPE) cells, induced differentiation of neural retina cells and related cytokine regulations. RPE cells can be derived from human embryonic stem cells (hESC) or Induced pluripotent stem cells (iPS). Recently hESC-derived RPE cells have been applied to patients with dry AMD with initial success in clinical trials. In terms of tissue engineering, studies are focused on factors affecting the long-term survival of transplanted cells, including tissue scaffolds, soluble hybrid materials and scaffold anchoring. This article briefly reviews the RPE differentiation, neural retina differentiation and related cytokines of cell-based therapy and scaffolds, materials, and cell-scaffolds interactions of tissue engineering in AMD treatment.

Citation： ShaoBing, ChenDi, MinHanyi. Progresses of cell-based therapy and tissue engineering in the treatment of age-related macular degeneration. Chinese Journal of Ocular Fundus Diseases, 2016, 32(1): 88-91. doi: 10.3760/cma.j.issn.1005-1015.2016.01.025 Copy

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7.	Gullapalli VK, Khodair MA, Wang H,et al. Retinalpigment epithelium and photo receptor transplantation frontiers [M]//Ryan SJ. Retina. Amsterdam: Elsevier, 2013:669-689.
8.	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. DOI: 10.1242/jcs.050393.
9.	Maruotti J, Wahlin K, Gorrell D,et al. A simple and scalable process for the differentiation of retinal pigment epithelium from human pluripotent stem cells [J]. Stem Cells Transl Med,2013,2(5):341-354. DOI: 10.5966/sctm.2012-0106.
10.	Schwartz SD, Regillo CD, Lam BL, et al. Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt's macular dystrophy: follow-up of two open-label phase 1/2 studies [J].Lancet, 2015, 385(9967):509-516. DOI: 10.1016/S0140-6736(14)61376-3.
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12.	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.
13.	Muñiz A,Ramesh KR,Greene WA,et al. Deriving retinal pigment epithelium (RPE) from induced pluripotent stem (iPS) cells by different sizes of embryoid bodies. J Vis Exp, 2015,96(2):E1. http://www.jove.com/video/52262/deriving-retinal-pigment-epithelium-rpe.from-induced-pluripo-tent-stem. DOI:10.3791/52262.
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15.	Philips MJ, Wallace KA, Dickerson SJ,et al. Blood-derived human iPS cells generate optic vesicle-like structures with the capacity to form retinal laminae and develop synapses [J].Invest Ophthalmol Vis Sci,2012,53(4):2007-2019. DOI: 10.1167/iovs.11-9313.
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17.	Boucherie C, Mukherjee S, Henckaerts E, et al. Brief report: self-organizing neuroepithelium from human pluripotent stem cells facilitates derivation of photoreceptors [J].Stem Cells,2013,31(2):408-414. DOI: 10.1002/stem.1268.
18.	Lamba DA, McUsic A, Hirata RK, et al. Generation, purification and transplantation of photoreceptors derived from human induced pluripotent stem cells. PLoS One, 2010,5(1):8763.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2808350/. DOI: 10.1371/journal.pone.0008763.
19.	Miller JW, Le Couter J, Strauss EC, et al. Vascular endothelial growth factor a in intraocular vascular disease [J].Ophthalmology,2013,120(1):106-114. DOI: 10.1016/j.ophtha.2012.07.038.
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22.	Falkner-Radler CI, Krebs I, Glittenberg C, et al. Human retinal pigment epithelium(RPE) transplantation: outcome after autologous RPE-choroid sheet and RPE cell-suspension in a randomised clinical study [J]. Br J Ophthalmol, 2011,95(3):370-375.DOI: 10.1136/bjo.2009.176305.
23.	Binder S. Scaffolds for retinal pigment epithelium replacement therapy [J]. Br J Ophthalmol, 2011,95(4):441-442. DOI: 10.1136/bjo.2009.171926.
24.	Nadri S, Yazdani S, Arefian E, et al. Mesenchymal stem cells from trabecular meshwork become photoreceptor-like cells on amniotic membrane [J].Neurosci Lett, 2013,541:43-48. DOI: 10.1016/j.neulet.2012.12.055.
25.	Thumann G, Viethen A, Gaebler A, et al.The in vitro and in vivo behaviour of retinal pigment epithelial cells cultured on ultrathin collagen membranes [J]. Biomaterials,2009,30(3):287-294. DOI: 10.1016/j.biomaterials.2008.09.039.
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28.	Yao J, Tao SL, Young MJ. Synthetic polymer scaffolds for stem cell transplantation in retinal tissue engineering [J]. Polymers, 2011,3(2): 899-914. DOI:10.3390/polym3020899.
29.	Treharne AJ,Thomson HA, Grossel MC, et al. Developing methacrylate-based copolymers as an artificial Bruch's membrane substitute [J].J Biomed Mater Res A, 2012,100(9):2358-2364. DOI: 10.1002/jbm.a.34178.
30.	Sistiabudi R, Paderi J, Panitch A, et al. Modification of native collagen with cell-adhesive peptide to promote RPE cell attachment on Bruch's membrane [J]. Biotechnol Bioeng, 2009,102(6):1723-1729. DOI: 10.1002/bit.22215.
31.	Carr AJ, Vugler AA, Hikita ST, et al. Protective effects of human iPS-derived retinal pigment epithelium cell transplantation in the retinal dystrophic rat. PLoS One, 2009,4(12):8152.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2780911/. DOI: 10.1371/journal.pone.0008152.
32.	Grafahrend D, Heffels KH, Beer MV, et al. Degradable polyester scaffoldswith controlled surface chemistry combining minimal protein adsorption with specific bioactivation [J].Nat Mater,2011,10(1):67-73. DOI: 10.1038/nmat2904.
33.	Bharti K, Rao M, Hull SC, et al. Developing cellular therapies for retinal degenerative diseases [J].Invest Ophthalmol Vis Sci,2014,55(2):1191-1202. DOI: 10.1167/iovs.13-13481.
34.	Key BW. Report of a Case of Transplantation of the Human Cornea [J]. Trans Am Ophthalmol Soc, 1930,28:29-41.
35.	Zweng HC, Flocks M, Kapany NS,et al.Experimental laser photocoagulation [J].Am J Ophthalmol,1964,58(9):353-362.
36.	Maguire AM, High KA, Auricchio A,et al. Age-dependent effects of RPE65 gene therapy for Leber's congenital amaurosis: a phase 1 dose-escalation trial [J]. Lancet, 2009,374(9701):1597-1605. DOI: 10.1016/S0140-6736(09)61836-5.

1. 张承芬,叶俊杰.年龄相关性黄斑变性[M]//张承芬.眼底病学.2版.北京:人民卫生出版社,2010:361-373.Zhang CF, Ye JJ. Age-related macular degeneration [M]//Zhang CF. Disease of ocular fundus. 2nd ed. Beijing: People's Medical Publishing House, 2010:361-373.
2. Fernández-Robredo P, Sancho A, Johnen S, et al.Current treatment limitations in age-related macular degeneration and future approaches based on cell therapy and tissue engineering.J Ophthalmol,2014,2014:510285. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941782/. DOI: 10.1155/2014/510285.
3. Casaroli-Marano RP, Zarbin MA. Cell-based therapy for retinal degenerative disease [M]. Basel: Karger, 2014:11-12. DOI: 10.1159/000359982.
4. Hunsberger J, Harrysson O, Shirwaiker R,et al. Manufacturing road map for tissue engineering and regenerative medicine technologies [J]. Stem Cells Transl Med,2015,4(2):130-135. DOI: 10.5966/sctm.2014-0254.
5. Lund RD, Wang S, Klimanskaya I,et al. Human embryonic stem-cell derived cells rescue visual function in dystrophic RSC rats [J]. Cloning Stem Cells, 2006, 8 (3):189-199.
6. Rowland TJ, Buchholz DE, Clegg DO. Pluripotent human stem cells for the treatment of retinal disease [J].J Cell Physiol,2012,227(2):457-466. DOI: 10.1002/jcp.22814.
7. Gullapalli VK, Khodair MA, Wang H,et al. Retinalpigment epithelium and photo receptor transplantation frontiers [M]//Ryan SJ. Retina. Amsterdam: Elsevier, 2013:669-689.
8. 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. DOI: 10.1242/jcs.050393.
9. Maruotti J, Wahlin K, Gorrell D,et al. A simple and scalable process for the differentiation of retinal pigment epithelium from human pluripotent stem cells [J]. Stem Cells Transl Med,2013,2(5):341-354. DOI: 10.5966/sctm.2012-0106.
10. Schwartz SD, Regillo CD, Lam BL, et al. Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt's macular dystrophy: follow-up of two open-label phase 1/2 studies [J].Lancet, 2015, 385(9967):509-516. DOI: 10.1016/S0140-6736(14)61376-3.
11. 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.DOI: 10.1016/j.cell.2006.07.024.
12. 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.
13. Muñiz A,Ramesh KR,Greene WA,et al. Deriving retinal pigment epithelium (RPE) from induced pluripotent stem (iPS) cells by different sizes of embryoid bodies. J Vis Exp, 2015,96(2):E1. http://www.jove.com/video/52262/deriving-retinal-pigment-epithelium-rpe.from-induced-pluripo-tent-stem. DOI:10.3791/52262.
14. Pera MF. Stem cells: the dark side of induced pluripotency [J].Nature, 2011, 471(7336):46-47. DOI: 10.1038/471046a.
15. Philips MJ, Wallace KA, Dickerson SJ,et al. Blood-derived human iPS cells generate optic vesicle-like structures with the capacity to form retinal laminae and develop synapses [J].Invest Ophthalmol Vis Sci,2012,53(4):2007-2019. DOI: 10.1167/iovs.11-9313.
16. Eiraku M, Takata N, Ishibashi H, et al. Self-organizing optic-cup morphogenesis in three-dimensional culture[J]. Nature,2011,472(7341):51-56. DOI: 10.1038/nature09941.
17. Boucherie C, Mukherjee S, Henckaerts E, et al. Brief report: self-organizing neuroepithelium from human pluripotent stem cells facilitates derivation of photoreceptors [J].Stem Cells,2013,31(2):408-414. DOI: 10.1002/stem.1268.
18. Lamba DA, McUsic A, Hirata RK, et al. Generation, purification and transplantation of photoreceptors derived from human induced pluripotent stem cells. PLoS One, 2010,5(1):8763.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2808350/. DOI: 10.1371/journal.pone.0008763.
19. Miller JW, Le Couter J, Strauss EC, et al. Vascular endothelial growth factor a in intraocular vascular disease [J].Ophthalmology,2013,120(1):106-114. DOI: 10.1016/j.ophtha.2012.07.038.
20. Kozulin P, Natoli R, Bumsted O'Brien KM, et al.The cellular expression of antiangiogenic factors in fetal primate macula[J].Invest Ophthalmol Vis Sci, 2010, 51(8):4298-4306. DOI: 10.1167/iovs.09-4905.
21. Hansson ML, Albert S, González Somermeyer L,et al. Efficient delivery and functional expression of transfected modified mRNA in human embryonic stem cell-derived retinal pigmented epithelial cells[J].J Biol Chem, 2015, 290(9):5661-5672. DOI: 10.1074/jbc.M114.618835.
22. Falkner-Radler CI, Krebs I, Glittenberg C, et al. Human retinal pigment epithelium(RPE) transplantation: outcome after autologous RPE-choroid sheet and RPE cell-suspension in a randomised clinical study [J]. Br J Ophthalmol, 2011,95(3):370-375.DOI: 10.1136/bjo.2009.176305.
23. Binder S. Scaffolds for retinal pigment epithelium replacement therapy [J]. Br J Ophthalmol, 2011,95(4):441-442. DOI: 10.1136/bjo.2009.171926.
24. Nadri S, Yazdani S, Arefian E, et al. Mesenchymal stem cells from trabecular meshwork become photoreceptor-like cells on amniotic membrane [J].Neurosci Lett, 2013,541:43-48. DOI: 10.1016/j.neulet.2012.12.055.
25. Thumann G, Viethen A, Gaebler A, et al.The in vitro and in vivo behaviour of retinal pigment epithelial cells cultured on ultrathin collagen membranes [J]. Biomaterials,2009,30(3):287-294. DOI: 10.1016/j.biomaterials.2008.09.039.
26. Hynes SR, Lavik EB. A tissue-engineered approach towards retinal repair: scaffolds for cell transplantation to the subretinal space [J].Graefe's Arch Clin Exp Ophthalmol, 2010,248(6):763-778. DOI: 10.1007/s00417-009-1263-7.
27. Stanzel BV, Liu Z, Brinken R, et al. Subretinal delivery of ultrathin rigid-elastic cell carriers using a metallic shooter instrument and biodegradable hydrogel encapsulation [J].Invest Ophthalmol Vis Sci, 2012,53(1):490-500. DOI: 10.1167/iovs.11-8260.
28. Yao J, Tao SL, Young MJ. Synthetic polymer scaffolds for stem cell transplantation in retinal tissue engineering [J]. Polymers, 2011,3(2): 899-914. DOI:10.3390/polym3020899.
29. Treharne AJ,Thomson HA, Grossel MC, et al. Developing methacrylate-based copolymers as an artificial Bruch's membrane substitute [J].J Biomed Mater Res A, 2012,100(9):2358-2364. DOI: 10.1002/jbm.a.34178.
30. Sistiabudi R, Paderi J, Panitch A, et al. Modification of native collagen with cell-adhesive peptide to promote RPE cell attachment on Bruch's membrane [J]. Biotechnol Bioeng, 2009,102(6):1723-1729. DOI: 10.1002/bit.22215.
31. Carr AJ, Vugler AA, Hikita ST, et al. Protective effects of human iPS-derived retinal pigment epithelium cell transplantation in the retinal dystrophic rat. PLoS One, 2009,4(12):8152.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2780911/. DOI: 10.1371/journal.pone.0008152.
32. Grafahrend D, Heffels KH, Beer MV, et al. Degradable polyester scaffoldswith controlled surface chemistry combining minimal protein adsorption with specific bioactivation [J].Nat Mater,2011,10(1):67-73. DOI: 10.1038/nmat2904.
33. Bharti K, Rao M, Hull SC, et al. Developing cellular therapies for retinal degenerative diseases [J].Invest Ophthalmol Vis Sci,2014,55(2):1191-1202. DOI: 10.1167/iovs.13-13481.
34. Key BW. Report of a Case of Transplantation of the Human Cornea [J]. Trans Am Ophthalmol Soc, 1930,28:29-41.
35. Zweng HC, Flocks M, Kapany NS,et al.Experimental laser photocoagulation [J].Am J Ophthalmol,1964,58(9):353-362.
36. Maguire AM, High KA, Auricchio A,et al. Age-dependent effects of RPE65 gene therapy for Leber's congenital amaurosis: a phase 1 dose-escalation trial [J]. Lancet, 2009,374(9701):1597-1605. DOI: 10.1016/S0140-6736(09)61836-5.

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Progresses of cell-based therapy and tissue engineering in the treatment of age-related macular degeneration

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