Directed differentiation of human embryonic stem cells into functional retinal pigment epithelium cells
Open accessAbstract
Dysfunction and loss of retinal pigment epithelium (RPE) leads to degeneration of photoreceptors in age-related macular degeneration and subtypes of retinitis pigmentosa. Human embryonic stem cells (hESCs) may serve as an unlimited source of RPE cells for transplantation in these blinding conditions. Here we show the directed differentiation of hESCs toward an RPE fate under defined culture conditions. We demonstrate that nicotinamide promotes the differentiation of hESCs to neural and subsequently to RPE fate. In the presence of nicotinamide, factors from the TGF-beta superfamily, which presumably pattern RPE development during embryogenesis, further direct RPE differentiation. The hESC-derived pigmented cells exhibit the morphology, marker expression, and function of authentic RPE and rescue retinal structure and function after transplantation to an animal model of retinal degeneration caused by RPE dysfunction. These results are an important step toward the future use of hESCs to replenish RPE in blinding diseases.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Published protocols using directed approaches provide relatively efficient differentiation into cultures of cells reported to possess a wide range of RPE characteristics, including gene expression, polarized organization, and physiological and cell biological functions.
“There are now published protocols using directed approaches that provide relatively efficient differentiation into cultures of cells, reported to possess a wide range of RPE characteristics, including gene expression, polarized organization, and physiological and cell biological functions (Idelson et al., 2009; Buchholz et al., 2013; Gong et al., 2015; Maruotti et al., 2015; Hazim et al., 2017).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Idelson et al., 2009
Cites
Embryonic Stem Cell Lines Derived from Human Blastocysts
Thomson, J. A., Itskovitz‐Eldor, J., Shapiro, S. S., Waknitz, M. A., Swiergiel, J. J., Marshall, V. S., & Jones, J. M. (1998) · Science · doi:10.1126/science.282.5391.1145 · Cited by 15,947 · see citing works
Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase
Imai, S.-I., Armstrong, C. M., Kaeberlein, M., & Guarente, L. (2000) · Nature · doi:10.1038/35001622 · Cited by 3,510 · see citing works
The Retinal Pigment Epithelium in Visual Function
Strauss, O. (2005) · Physiological Reviews · doi:10.1152/physrev.00021.2004 · Cited by 2,828 · see citing works
Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro
Reubinoff, B. E., Pera, M. F., Fong, C., Trounson, A. O., & Bongso, A. (2000) · Nature Biotechnology · doi:10.1038/74447 · Cited by 2,708 · see citing works
Self-citationInman, G. J., Nicolás, F. J., Callahan, J. F., Harling, J. D., Gaster, L. M., Reith, A. D., Laping, N. J., & Hill, C. S. (2002) · Molecular Pharmacology · doi:10.1124/mol.62.1.65 · Cited by 1,636 · see citing works
Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat
D'Cruz, P. M. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.4.645 · Cited by 869 · see citing works
Osakada, F., Ikeda, H. O., Mandai, M., Wataya, T., Watanabe, K., Yoshimura, N., Akaike, A., Sasai, Y., & Takahashi, M. (2008) · Nature Biotechnology · doi:10.1038/nbt1384 · Cited by 629 · see citing works
Sirt1 contributes critically to the redox-dependent fate of neural progenitors
Prozorovski, T., Schulze-Topphoff, U., Glumm, R., Baumgart, J., Schröter, F., Ninnemann, O., Siegert, E., Bendix, I., Brüstle, O., Nitsch, R., et al. (2008) · Nature Cell Biology · doi:10.1038/ncb1700 · Cited by 451 · see citing works
Klimanskaya, I. V., Hipp, J., Rezai, K. A., West, M. D., Atala, A., & Lanza, R. (2004) · Cloning and Stem Cells · doi:10.1089/clo.2004.6.217 · Cited by 440 · see citing works
Human Embryonic Stem Cell–Derived Cells Rescue Visual Function in Dystrophic RCS Rats
Lund, R. D., Wang, S., Klimanskaya, I. V., Holmes, T. M., Ramos-Kelsey, R., Lü, B., Girman, S. V., Bischoff, N., Sauvé, Y., & Lanza, R. (2006) · Cloning and Stem Cells · doi:10.1089/clo.2006.8.189 · Cited by 407 · see citing works
Drăghici, S. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg624 · Cited by 356 · see citing works
Tao, W., Wen, R., Goddard, M. B., Sherman, S., O'Rourke, P., Stabila, P. F., Bell, W. J., Dean, B. J., Kauper, K. A., Budz, V. A., et al. (2002) · PubMed · Cited by 325 · see citing works
Pankratz, M. T., Li, X.-J., LaVaute, T. M., Lyons, E. A., Chen, X., & Zhang, S. (2007) · Stem Cells · doi:10.1634/stemcells.2006-0707 · Cited by 315 · see citing works
Fuhrmann, S., Levine, E. M., & Reh, T. A. (2000) · Development · doi:10.1242/dev.127.21.4599 · Cited by 285 · see citing works
Vugler, A., Carr, A. F., Lawrence, J. M., Chen, L., Burrell, K. E., Wright, A., von Leithner, P. L., Semo, M., Ahmado, A., Gias, C., et al. (2008) · Experimental Neurology · doi:10.1016/j.expneurol.2008.09.007 · Cited by 272 · see citing works
Eye development: a view from the retina pigmented epithelium
Martínez‐Morales, J. R., Rodrigo, I., & Bovolenta, P. (2004) · BioEssays · doi:10.1002/bies.20064 · Cited by 271 · see citing works
Stable genetic modification of human embryonic stem cells by lentiviral vectors
Gropp, M., Itsykson, P., Singer, O., Ben‐Hur, T., Reinhartz, E., Galun, E., & Reubinoff, B. E. (2003) · Molecular Therapy · doi:10.1016/s1525-0016(02)00047-3 · Cited by 248 · see citing works
Self-citationOtonkoski, T., Beattie, G. M., Mally, M. I., Ricordi, C., & Hayek, A. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116723 · Cited by 244 · see citing works
RPE transplantation and its role in retinal disease
da Cruz, L., Chen, F. K., Ahmado, A., Greenwood, J., & Coffey, P. J. (2007) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2007.07.001 · Cited by 238 · see citing works
Haruta, M., Sasai, Y., Kawasaki, H., Amemiya, K., Ooto, S., Kitada, M., Suemori, H., Nakatsuji, N., Idé, C., Honda, Y., et al. (2004) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.03-1034 · Cited by 212 · see citing works
Long-term preservation of cortically dependent visual function in RCS rats by transplantation
Coffey, P. J., Girman, S., Wang, S. M., Hetherington, L., Keegan, D., Adamson, P., Greenwood, J., & Lund, R. D. (2001) · Nature Neuroscience · doi:10.1038/nn782 · Cited by 198 · see citing works
Paquet‐Durand, F., Silva, J., Talukdar, T., Johnson, L. E., Azadi, S., Veen, T. V., Ueffing, M., Hauck, S. M., & Ekström, P. A. R. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.1514-07.2007 · Cited by 140 · see citing works
Cell Life Versus Cell Longevity: The Mysteries Surrounding the NAD+ Precursor Nicotinamide
Li, F., Chong, Z. Z., & Maiese, K. (2006) · Current Medicinal Chemistry · doi:10.2174/092986706776361058 · Cited by 127 · see citing works
Chong, Z. Z., Lin, S., Li, F., & Maiese, K. (2005) · Current Neurovascular Research · doi:10.2174/156720205774322584 · Cited by 126 · see citing works
Little, C. W., Castillo, B. V., DiLoreto, D. A., Cox, C., Wyatt, J. D., del Cerro, C., & del Cerro, M. (1996) · PubMed · Cited by 115 · see citing works
Formation of human prostate tissue from embryonic stem cells
Taylor, R. A., Cowin, P. A., Cunha, G. R., Pera, M. F., Trounson, A. O., Pedersen, J., & Risbridger, G. P. (2006) · Nature Methods · doi:10.1038/nmeth855 · Cited by 108 · see citing works
Sauvé, Y., Girman, S., Wang, S., Keegan, D., & Lund, R. D. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00271-3 · Cited by 74 · see citing works
Ben‐Dor, I., Itsykson, P., Goldenberg, D., Galun, E., & Reubinoff, B. E. (2006) · Molecular Therapy · doi:10.1016/j.ymthe.2006.02.010 · Cited by 60 · see citing works
Self-citationAoki, H., Hara, A., Nakagawa, S., Motohashi, T., Hirano, M., Takahashi, Y., & Kunisada, T. (2005) · Experimental Eye Research · doi:10.1016/j.exer.2005.06.021 · Cited by 60 · see citing works
Shen, C., Huang, H., Ou, H., Chen, H., Chen, W., & Jeng, K.-C. G. (2004) · Journal of Biomedical Science · doi:10.1007/bf02256096 · Cited by 54 · see citing works
Identification of a Functional Binding Site for Activin on the Type I Receptor ALK4
Harrison, C. A., Gray, P. C., Koerber, S. C., Fischer, W. H., & Vale, W. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m302015200 · Cited by 53 · see citing works
Transplantable retinal pigment epithelial cell sheets for tissue engineering
Kubota, A., Nishida, K., Yamato, M., Yang, J., Kikuchi, A., Okano, T., & Tano, Y. (2006) · Biomaterials · doi:10.1016/j.biomaterials.2006.02.018 · Cited by 44 · see citing works
Embryonic Stem Cells: Potential Source for Ocular Repair
Haruta, M., & Takahashi, M. (2005) · Seminars in Ophthalmology · doi:10.1080/08820530590921846 · Cited by 39 · see citing works
Photoreceptor repair in response to RPE transplants in RCS rats: Outer segment regeneration
Lin, N., Fan, W., Sheedlo, H. J., Aschenbrenner, J. E., & Turner, J. E. (1996) · Current Eye Research · doi:10.3109/02713689609017657 · Cited by 36 · see citing works
Nicotinamide Rescues Human Embryonic Stem Cell-Derived Neuroectoderm from Parthanatic Cell Death
Cimadamore, F., Curchoe, C. L., Alderson, N. B., Scott, F. L., Salvesen, G. S., & Terskikh, A. V. (2009) · Stem Cells · doi:10.1002/stem.107 · Cited by 34 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Self-formation of optic cups and storable stratified neural retina from human ESCs
Nakano, T., Ando, S., Takata, N., Kawada, M., Muguruma, K., Sekiguchi, K., Saito, K., Yonemura, S., Eiraku, M., & Sasai, Y. (2012) · Cell stem cell · doi:10.1016/j.stem.2012.05.009 · Cited by 1,447 · see citing works
da Cruz, L., Fynes, K., Georgiadis, O., Kerby, J., Luo, Y. H.-L., Ahmado, A., Vernon, A. J., Daniels, J. T., Nommiste, B., Hasan, S. M., et al. (2018) · Nature Biotechnology · doi:10.1038/nbt.4114 · Cited by 714 · see citing works
Photoreceptor degeneration: genetic and mechanistic dissection of a complex trait
Wright, A. F., Chakarova, C. F., El-Aziz, M. M. A., & Bhattacharya, S. S. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2717 · Cited by 632 · see citing works
Meyer, J. S., Howden, S. E., Wallace, K. A., Verhoeven, A. D., Wright, L. S., Capowski, E. E., Pinilla, I., Martin, J. M., Tian, S., Stewart, R. M., et al. (2011) · Stem Cells · doi:10.1002/stem.674 · Cited by 464 · see citing works
The cell biology of the retinal pigment epithelium
Lakkaraju, A., Umapathy, A., Tan, L. X., Daniele, L., Philp, N. J., Boesze-Battaglia, K., & Williams, D. S. (2020) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2020.100846 · Cited by 422 · see citing works
Carr, A. F., Vugler, A., Hikita, S. T., Lawrence, J. M., Gias, C., Chen, L., Buchholz, D. E., Ahmado, A., Semo, M., Smart, M. J. K., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0008152 · Cited by 412 · see citing works
Cuenca, N., Fernández-Sánchez, L., Campello, L., Maneu, V., De la Villa, P., Lax, P., & Pinilla, I. (2014) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2014.07.001 · Cited by 401 · see citing works
Sharma, R., Khristov, V., Rising, A. C., Jha, B. S., Dejene, R., Hotaling, N. A., Li, Y., Stoddard, J., Stankewicz, C., Wan, Q., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aat5580 · Cited by 362 · see citing works
Generation of a ciliary margin-like stem cell niche from self-organizing human retinal tissue
Kuwahara, A., Ozone, C., Nakano, T., Saito, K., Eiraku, M., & Sasai, Y. (2015) · Nature Communications · doi:10.1038/ncomms7286 · Cited by 353 · see citing works
From confluent human iPS cells to self-forming neural retina and retinal pigmented epithelium
Reichman, S., Terray, A., Slembrouck-Brec, A., Nanteau, C., Orieux, G., Habeler, W., Nandrot, E. F., Sahel, J., Monville, C., & Goureau, O. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1324212111 · Cited by 304 · see citing works
Turning straw into gold: directing cell fate for regenerative medicine
Cohen, D. E., & Melton, D. (2011) · Nature reviews genetics · doi:10.1038/nrg2938 · Cited by 283 · see citing works
NAD metabolism: Implications in aging and longevity
Yaku, K., Okabe, K., & Nakagawa, T. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.05.006 · Cited by 269 · see citing works
Transcriptome analysis and molecular signature of human retinal pigment epithelium
Strunnikova, N. V., Maminishkis, A., Barb, J. J., Wang, F., Zhi, C., Sergeev, Y., Chen, W., Edwards, A. O., Stambolian, D., Abecasis, G., et al. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq129 · Cited by 269 · see citing works
Buchholz, D. E., Pennington, B. O., Croze, R. H., Hinman, C. R., Coffey, P. J., & Clegg, D. O. (2013) · Stem Cells Translational Medicine · doi:10.5966/sctm.2012-0163 · Cited by 261 · see citing works
Adult Human RPE Can Be Activated into a Multipotent Stem Cell that Produces Mesenchymal Derivatives
Salero, E., Blenkinsop, T. A., Corneo, B., Harris, A., Rabin, D. M., Stern, J. H., & Temple, S. (2012) · Cell stem cell · doi:10.1016/j.stem.2011.11.018 · Cited by 259 · see citing works
Mica, Y., Lee, G., Chambers, S. M., Tomishima, M. J., & Studer, L. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.03.025 · Cited by 257 · see citing works
Stem cells in retinal regeneration: past, present and future
Ramsden, C. M., Powner, M. B., Carr, A. F., Smart, M. J. K., da Cruz, L., & Coffey, P. J. (2013) · Development · doi:10.1242/dev.092270 · Cited by 254 · see citing works
Reichman, S., Slembrouck-Brec, A., Gagliardi, G., Chaffiol, A., Terray, A., Nanteau, C., Potey, A., Belle, M., Rabesandratana, O., Duebel, J., et al. (2017) · Stem Cells · doi:10.1002/stem.2586 · Cited by 241 · see citing works
Biology and therapy of inherited retinal degenerative disease: insights from mouse models
Veleri, S., Lazar, C. H., Chang, B., Sieving, P. A., Banin, E., & Swaroop, A. (2015) · Disease Models & Mechanisms · doi:10.1242/dmm.017913 · Cited by 232 · see citing works
Self-citationRetinal stem cell transplantation: Balancing safety and potential
Singh, M. S., Park, S. S., Albini, T. A., Canto-Soler, M. V., Klassen, H. J., MacLaren, R. E., Takahashi, M., Nagiel, A., Schwartz, S. D., & Bharti, K. (2019) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2019.100779 · Cited by 225 · see citing works
Stemming retinal regeneration with pluripotent stem cells
Jin, Z., Gao, M.-L., Deng, W.-L., Wu, K., Sugita, S., Mandai, M., & Takahashi, M. (2018) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2018.11.003 · Cited by 218 · see citing works
Stem cell based therapies for age-related macular degeneration: The promises and the challenges
Nazari, H. K., Zhang, L., Zhu, D., Chader, G. J., Falabella, P., Stefanini, F. R., Rowland, T. J., Clegg, D., Kashani, A. H., Hinton, D. R., et al. (2015) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2015.06.004 · Cited by 207 · see citing works
Molecular signature of primary retinal pigment epithelium and stem-cell-derived RPE cells
Liao, J., Yu, J., Huang, K. Y., Hu, J. G., Diemer, T., Ma, Z., Dvash, T., Yang, X.-J., Travis, G. H., Williams, D. S., et al. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq341 · Cited by 188 · see citing works
Kokkinaki, M., Sahibzada, N., & Golestaneh, N. (2011) · Stem Cells · doi:10.1002/stem.635 · Cited by 180 · see citing works
A Systematic Approach to Identify Candidate Transcription Factors that Control Cell Identity
D’Alessio, A. C., Fan, Z. P., Wert, K. J., Baranov, P., Cohen, M. A., Saini, J. S., Cohick, E., Charniga, C., Dadon, D., Hannett, N. M., et al. (2015) · Stem Cell Reports · doi:10.1016/j.stemcr.2015.09.016 · Cited by 172 · see citing works
Self-citationThe retinal pigment epithelium: An important player of retinal disorders and regeneration
Chiba, C. (2013) · Experimental Eye Research · doi:10.1016/j.exer.2013.07.009 · Cited by 172 · see citing works
Development of human embryonic stem cell therapies for age-related macular degeneration
Carr, A. F., Smart, M. J. K., Ramsden, C. M., Powner, M. B., da Cruz, L., & Coffey, P. J. (2013) · Trends in Neurosciences · doi:10.1016/j.tins.2013.03.006 · Cited by 166 · see citing works
Vaajasaari, H., Ilmarinen, T., Juuti‐Uusitalo, K., Rajala, K. M., Onnela, N., Narkilahti, S., Suuronen, R., Hyttinen, J., Uusitalo, H. M. T., & Skottman, H. (2011) · PubMed Central · Cited by 152 · see citing works
Bharti, K., Miller, S. S., & Arnheiter, H. (2010) · Pigment Cell & Melanoma Research · doi:10.1111/j.1755-148x.2010.00772.x · Cited by 147 · see citing works
Specification of neuronal and glial subtypes from human pluripotent stem cells
Liu, H., & Zhang, S. (2011) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-011-0770-y · Cited by 142 · see citing works
Maruotti, J., Sripathi, S. R., Bharti, K., Fuller, J., Wahlin, K. J., Jaskula-Ranga, V., Sluch, V. M., Berlinicke, C. A., Davis, J. A., Kim, C., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1422818112 · Cited by 143 · see citing works
Tzameret, A., Sher, I., Belkin, M., Treves, A. J., Meir, A., Nagler, A., Levkovitch-Verbin, H., Barshack, I., Rosner, M., & Rotenstreich, Y. (2013) · Experimental Eye Research · doi:10.1016/j.exer.2013.10.023 · Cited by 137 · see citing works
Sluch, V. M., Chamling, X., Liu, M. M., Berlinicke, C. A., Cheng, J., Mitchell, K. L., Welsbie, D. S., & Zack, D. J. (2017) · Stem Cells Translational Medicine · doi:10.1002/sctm.17-0059 · Cited by 132 · see citing works
Course of Sodium Iodate–Induced Retinal Degeneration in Albino and Pigmented Mice
Chowers, G., Cohen, M. J., Marks-Ohana, D., Stika, S., Eijzenberg, A., Banin, E., & Obolensky, A. (2017) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.16-21255 · Cited by 130 · see citing works
Self-citationRapid differentiation of the human RPE cell line, ARPE-19, induced by nicotinamide
Hazim, R. A., Volland, S., Yen, A., Burgess, B. L., & Williams, D. S. (2019) · Experimental Eye Research · doi:10.1016/j.exer.2018.10.009 · Cited by 126 · see citing works
“Given the role that nicotinamide has been shown to play in the differentiation of RPE from pluripotent stem cells (Idelson et al., 2009; Maruotti et al., 2015; Saini et al., 2017), we tested the necessity of nicotinamide in the MEM-Nic medium for the observed morphological phenotype.”
BackgroundGropp, M., Shilo, V., Vainer, G. W., Gov, M., Gil, Y., Khaner, H., Matzrafi, L., Idelson, M., Kopolovic, J., Zak, N. B., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0045532 · Cited by 125 · see citing works
Self-citationPlasma membrane protein polarity and trafficking in RPE cells: past, present and future
Lehmann, G. L., Benedicto, I., Philp, N. J., & Rodriguez-Boulan, E. (2014) · Experimental Eye Research · doi:10.1016/j.exer.2014.04.021 · Cited by 122 · see citing works
Zhu, D., Deng, X., Spee, C. K., Sonoda, S., Hsieh, C., Barrón, E., Pera, M. F., & Hinton, D. R. (2010) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.10-6413 · Cited by 119 · see citing works
TGF-β Family Signaling in Epithelial Differentiation and Epithelial–Mesenchymal TransitionPreprint
Kahata, K., Dadras, M. S., & Moustakas, A. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a022194 · Cited by 119 · see citing works
Oxidative stress: Biomarkers and novel therapeutic pathways
Maiese, K., Chong, Z. Z., Hou, J., & Shang, Y. (2010) · Experimental Gerontology · doi:10.1016/j.exger.2010.01.004 · Cited by 116 · see citing works
Hongisto, H., Ilmarinen, T., Vattulainen, M., Mikhailova, A., & Skottman, H. (2017) · Stem Cell Research & Therapy · doi:10.1186/s13287-017-0738-4 · Cited by 115 · see citing works
Zhao, J. J., & Afshari, N. A. (2016) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.16-20024 · Cited by 112 · see citing works
Zhou, S., Flamier, A., Abdouh, M., Tétreault, N., Barabino, A., Wadhwa, S., & Bernier, G. (2015) · Development · doi:10.1242/dev.125385 · Cited by 110 · see citing works
M’Barek, K. B., Habeler, W., Plancheron, A., Jarraya, M., Régent, F., Terray, A., Yang, Y., Chatrousse, L., Domingues, S., Masson, Y., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aai7471 · Cited by 111 · see citing works
Regenerative and restorative medicine for eye disease
Gelder, R. N. V., Chiang, M. F., Dyer, M. A., Greenwell, T. N., Levin, L. A., Wong, R., & Svendsen, C. N. (2022) · Nature Medicine · doi:10.1038/s41591-022-01862-8 · Cited by 110 · see citing works
Yang, C., Yang, Y., Brennan, L., Bouhassira, E. E., Kantorow, M., & Cvekl, A. (2010) · The FASEB Journal · doi:10.1096/fj.10-157255 · Cited by 110 · see citing works
Cell-based therapeutic strategies for replacement and preservation in retinal degenerative diseases
Jones, M. K., Lü, B., Girman, S., & Wang, S. (2017) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2017.01.004 · Cited by 110 · see citing works
Radeke, M. J., Radeke, C. M., Shih, Y.-H., Hu, J. G., Bok, D., Johnson, L. V., & Coffey, P. J. (2015) · Genome Medicine · doi:10.1186/s13073-015-0183-x · Cited by 109 · see citing works
Zhu, Y., Carido, M., Meinhardt, A., Kurth, T., Karl, M., Ader, M., & Tanaka, E. M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0054552 · Cited by 106 · see citing works
Jenkins, M. J., & Farid, S. S. (2014) · Biotechnology Journal · doi:10.1002/biot.201400348 · Cited by 107 · see citing works
Jarrige, M., Frank, E., Herardot, E., Martineau, S., Darle, A., Benabidès, M., Domingues, S., Chose, O., Habeler, W., Lorant, J., et al. (2021) · Cells · doi:10.3390/cells10020240 · Cited by 106 · see citing works
Rowland, T. J., Blaschke, A. J., Buchholz, D. E., Hikita, S. T., Johnson, L. V., & Clegg, D. (2012) · Journal of Tissue Engineering and Regenerative Medicine · doi:10.1002/term.1458 · Cited by 101 · see citing works
Meng, Y., Ren, Z., Xu, F., Zhou, X., Song, C., Wang, V. Y., Liu, W., Lu, L., Thomson, J. A., & Chen, G. (2018) · Stem Cell Reports · doi:10.1016/j.stemcr.2018.10.023 · Cited by 100 · see citing works
Maruotti, J., Wahlin, K. J., Gorrell, D., Bhutto, I. A., Lutty, G. A., & Zack, D. J. (2013) · Stem Cells Translational Medicine · doi:10.5966/sctm.2012-0106 · Cited by 96 · see citing works
Retinal pigment epithelial cell proliferation
Stern, J. H., & Temple, S. (2015) · Experimental Biology and Medicine · doi:10.1177/1535370215587530 · Cited by 94 · see citing works
Stem Cell-Based Therapeutic Applications in Retinal Degenerative Diseases
Huang, Y., Enzmann, V., & Ildstad, S. T. (2010) · Stem Cell Reviews and Reports · doi:10.1007/s12015-010-9192-8 · Cited by 94 · see citing works
Bharti, K., den Hollander, A. I., Lakkaraju, A., Sinha, D., Williams, D. S., Finnemann, S. C., Rickman, C. B., Malek, G., & D'Amore, P. A. (2022) · Experimental Eye Research · doi:10.1016/j.exer.2022.109170 · Cited by 92 · see citing works
Nasonkin, I. O., Merbs, S. L., Lazo, K., Oliver, V. F., Brooks, M., Patel, K., Enke, R. A., Nellissery, J. K., Jamrich, M., Le, Y. Z., et al. (2013) · Development · doi:10.1242/dev.086603 · Cited by 90 · see citing works
Sharma, R., Bose, D., Maminishkis, A., & Bharti, K. (2020) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010919-023245 · Cited by 91 · see citing works
Pluripotent human stem cells for the treatment of retinal disease
Rowland, T. J., Buchholz, D. E., & Clegg, D. (2011) · Journal of Cellular Physiology · doi:10.1002/jcp.22814 · Cited by 90 · see citing works
Régent, F., Morizur, L., Lesueur, L., Habeler, W., Plancheron, A., M’Barek, K. B., & Monville, C. (2019) · Scientific Reports · doi:10.1038/s41598-019-47123-6 · Cited by 89 · see citing works
Krohne, T. U., Westenskow, P. D., Kurihara, T., Friedlander, D. F., Lehmann, M. D., Dorsey, A. L., Li, W., Zhu, S., Schultz, A. W., Wang, J., et al. (2012) · Stem Cells Translational Medicine · doi:10.5966/sctm.2011-0057 · Cited by 87 · see citing works
Raviv, S., Bharti, K., Rencus‐Lazar, S., Cohen‐Tayar, Y., Schyr, R. B., Evantal, N., Meshorer, E., Zilberberg, A., Idelson, M., Reubinoff, B. E., et al. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004360 · Cited by 88 · see citing works
Self-citationLi, Y., Wu, W.-H., Hsu, C.-W., Nguyen, H. V., Tsai, Y., Chan, L., Nagasaki, T., Maumenee, I. H., Yannuzzi, L. A., Hoang, Q. V., et al. (2014) · Molecular Therapy · doi:10.1038/mt.2014.100 · Cited by 84 · see citing works
Adult Neural Stem Cells: Response to Stroke Injury and Potential for Therapeutic Applications
Barkho, B. Z., & Zhao, X. (2011) · Current Stem Cell Research & Therapy · doi:10.2174/157488811797904362 · Cited by 83 · see citing works
Wang, N.-K., Tosi, J., Kasanuki, J. M., Chou, C. L., Kong, J., Parmalee, N. L., Wert, K. J., Allikmets, R. L., Lai, C.-C., Chien, C.-L., et al. (2010) · Transplantation · doi:10.1097/tp.0b013e3181d45a61 · Cited by 82 · see citing works
Pouya, A., Satarian, L., Kiani, S., Javan, M., & Baharvand, H. (2011) · PLoS ONE · doi:10.1371/journal.pone.0027925 · Cited by 80 · see citing works
Immunological aspects of RPE cell transplantation
Sugita, S., Mandai, M., Kamao, H., & Takahashi, M. (2021) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2021.100950 · Cited by 77 · see citing works
Comparison of FRPE and Human Embryonic Stem Cell–Derived RPE Behavior on Aged Human Bruch's Membrane
Sugino, I. K., Sun, Q., Wang, J., Nunes, C. F., Cheewatrakoolpong, N., Rapista, A., Johnson, A. C., Malcuit, C. M., Klimanskaya, I. V., Lanza, R., et al. (2011) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.10-5386 · Cited by 76 · see citing works
ROCK Inhibition Extends Passage of Pluripotent Stem Cell-Derived Retinal Pigmented Epithelium
Croze, R. H., Buchholz, D. E., Radeke, M. J., Thi, W. J., Hu, Q., Coffey, P. J., & Clegg, D. (2014) · Stem Cells Translational Medicine · doi:10.5966/sctm.2014-0079 · Cited by 76 · see citing works
Achberger, K., Haderspeck, J. C., Kleger, A., & Liebau, S. (2019) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2018.05.005 · Cited by 75 · see citing works
Reyes, Á. P., Petrus-Reurer, S., Antonsson, L., Stenfelt, S., Bartuma, H., Panula, S., Mader, T., Douagi, I., André, H., Hovatta, O., et al. (2015) · Stem Cell Reports · doi:10.1016/j.stemcr.2015.11.008 · Cited by 74 · see citing works
Relaxation‐expansion model for self‐driven retinal morphogenesis
Eiraku, M., ADACHI, T., & Sasai, Y. (2011) · BioEssays · doi:10.1002/bies.201100070 · Cited by 74 · see citing works
Zahabi, A., Shahbazi, E., Ahmadieh, H., Hassani, S., Totonchi, M., Taei, A., Masoudi, N., Ebrahimi, M., Aghdami, N., Seifinejad, A., et al. (2011) · Stem Cells and Development · doi:10.1089/scd.2011.0599 · Cited by 74 · see citing works
Dahlmann-Noor, A. H., Vijay, S., Jayaram, H., Limb, G. A., & Khaw, P. T. (2010) · Canadian Journal of Ophthalmology · doi:10.3129/i10-077 · Cited by 74 · see citing works
Nissan, X., Larribère, L., Saidani, M., Hurbain, I., Delevoye, C., Feteira, J., Lemaı̂tre, G., Peschanski, M., & Baldeschi, C. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1019070108 · Cited by 75 · see citing works
Thomas, B. B., Zhu, D., Zhang, L., Thomas, P. B., Hu, Y., Nazari, H. K., Stefanini, F. R., Falabella, P., Clegg, D., Hinton, D. R., et al. (2016) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.16-19238 · Cited by 74 · see citing works
Using human induced pluripotent stem cells to treat retinal disease
Borooah, S., Phillips, M. J., Bilican, B., Wright, A. F., Wilmut, I., Chandran, S., Gamm, D. M., & Dhillon, B. (2013) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2013.09.002 · Cited by 71 · see citing works
Petrus-Reurer, S., Winblad, N., Kumar, P., Gorchs, L., Chrobok, M., Wagner, A. K., Bartuma, H., Lardner, E., Aronsson, M., Reyes, Á. P., et al. (2020) · Stem Cell Reports · doi:10.1016/j.stemcr.2020.02.006 · Cited by 72 · see citing works
Sorkio, A., Vuorimaa, E., Hakola, H. M., Liang, H., Ujula, T., Valle‐Delgado, J. J., Österberg, M., Yliperttula, M. L., & Skottman, H. (2015) · Biomaterials · doi:10.1016/j.biomaterials.2015.02.005 · Cited by 72 · see citing works
Generation of hESC-derived retinal pigment epithelium on biopolymer coated polyimide membranes
Subrizi, A., Hiidenmaa, H., Ilmarinen, T., Nymark, S., Dubruel, P., Uusitalo, H. M. T., Yliperttula, M. L., Urtti, A. O., & Skottman, H. (2012) · Biomaterials · doi:10.1016/j.biomaterials.2012.07.033 · Cited by 72 · see citing works
McGill, T. J., Stoddard, J., Renner, L. M., Messaoudi, I., Bharti, K., Mitalipov, S. M., Lauer, A. K., Wilson, D. J., & Neuringer, M. (2018) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.17-22467 · Cited by 72 · see citing works
Cellular models and therapies for age-related macular degeneration
Forest, D. L., Johnson, L. V., & Clegg, D. (2015) · Disease Models & Mechanisms · doi:10.1242/dmm.017236 · Cited by 69 · see citing works
High-throughput physical phenotyping of cell differentiation
Lin, J., Kim, D., Tse, H. T. K., Tseng, P., Peng, L. T., Dhar, M., Karumbayaram, S., & Carlo, D. D. (2017) · Microsystems & Nanoengineering · doi:10.1038/micronano.2017.13 · Cited by 69 · see citing works
Stem Cell Treatment in Retinal Diseases: Recent Developments
Öner, A. (2018) · Turkish Journal of Ophthalmology · doi:10.4274/tjo.89972 · Cited by 68 · see citing works
Expanding the boundaries of embryonic stem cells.
Ben-David, U., Kopper, O., & Benvenisty, N. (2012) · Cell Stem Cell · doi:10.1016/j.stem.2012.05.003 · Cited by 69 · see citing works
Sorkio, A., Hongisto, H., Kaarniranta, K., Uusitalo, H. M. T., Juuti‐Uusitalo, K., & Skottman, H. (2013) · Tissue Engineering Part A · doi:10.1089/ten.tea.2013.0049 · Cited by 67 · see citing works
Hazim, R. A., Karumbayaram, S., Jiang, M., Dimashkie, A., Lopes, V. S., Li, D., Burgess, B. L., Vijayaraj, P., Alva-Ornelas, J. A., Zack, J. A., et al. (2017) · Stem Cell Research & Therapy · doi:10.1186/s13287-017-0652-9 · Cited by 66 · see citing works
Stem cells as source for retinal pigment epithelium transplantation
Bertolotti, E., Neri, A., Camparini, M., Macaluso, C., & Marigo, V. (2014) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2014.06.002 · Cited by 66 · see citing works
Stem cell therapy for retinal disease
Tibbetts, M. D., Samuel, M. A., Chang, T. S., & Ho, A. C. (2012) · Current Opinion in Ophthalmology · doi:10.1097/icu.0b013e328352407d · Cited by 65 · see citing works
Chemical strategies for stem cell biology and regenerative medicine.
Zhu, S.-Y., Wei, W.-G., & Ding, S. (2011) · Annual Review of Biomedical Engineering · doi:10.1146/annurev-bioeng-071910-124715 · Cited by 66 · see citing works
Singh, R. K., & Nasonkin, I. O. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00179 · Cited by 66 · see citing works
Induced pluripotent stem cells as custom therapeutics for retinal repair: Progress and rationale
Wright, L. S., Phillips, M. J., Pinilla, I., Hei, D. J., & Gamm, D. M. (2014) · Experimental Eye Research · doi:10.1016/j.exer.2013.12.001 · Cited by 65 · see citing works
Pluripotent Stem Cells for Retinal Tissue Engineering: Current Status and Future Prospects
Singh, R. K., Cuzzani, O., Binette, F., Sternberg, H., West, M. D., & Nasonkin, I. O. (2018) · Stem Cell Reviews and Reports · doi:10.1007/s12015-018-9802-4 · Cited by 63 · see citing works
Characterization of a Mouse Model With Complete RPE Loss and Its Use for RPE Cell Transplantation
Carido, M., Zhu, Y., Postel, K., Benkner, B., Cimalla, P., Karl, M., Kurth, T., Paquet‐Durand, F., Koch, E., Münch, T. A., et al. (2014) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.14-14325 · Cited by 63 · see citing works
Stem Cell Therapies for Reversing Vision Loss
Higuchi, A., Kumar, S. S., Benelli, G., Alarfaj, A. A., Munusamy, M. A., Umezawa, A., & Murugan, K. (2017) · Trends in biotechnology · doi:10.1016/j.tibtech.2017.06.016 · Cited by 63 · see citing works
Serine biosynthesis defect due to haploinsufficiency of PHGDH causes retinal disease
Eade, K., Gantner, M. L., Hostyk, J. A., Nagasaki, T., Giles, S., Fallon, R. J., Harkins-Perry, S. R., Baldini, M., Lim, E. W., Scheppke, L., et al. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00361-3 · Cited by 61 · see citing works
Sorsby fundus dystrophy—A review of pathology and disease mechanisms
Christensen, D. R. G., Brown, F. E., Cree, A. J., Ratnayaka, J. A., & Lotery, A. J. (2017) · Experimental Eye Research · doi:10.1016/j.exer.2017.08.014 · Cited by 60 · see citing works
Song, M. J., & Bharti, K. (2015) · Brain Research · doi:10.1016/j.brainres.2015.12.011 · Cited by 59 · see citing works
Petrus-Reurer, S., Bartuma, H., Aronsson, M., Westman, S., Lanner, F., André, H., & Kvanta, A. (2017) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.16-20738 · Cited by 59 · see citing works
- Authors
- Idelson, M., Alper, R., Obolensky, A., Ben-Shushan, E., Hemo, I., Yachimovich-Cohen, N., Khaner, H., Smith, Y., Wiser, O., Gropp, M., Cohen, M. A., Even-Ram, S., Berman-Zaken, Y., Matzrafi, L., Rechavi, G., Banin, E., & Reubinoff, B.
- Affiliations
- Hebrew University of Jerusalem (IL)
- Hadassah Medical Center (IL)
- Sheba Medical Center (IL)
- Corresponding author
- Reubinoff, Benjamin
- Venue
- Cell stem cell
- Publisher
- Elsevier BV
- Published
- 2009-10
- Volume
- 5
- Issue
- 4
- Pages
- 396-408
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W2092167465
- Cited by
- 486
- References
- 35
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 19 · 2023: 16 · 2022: 23 · 2021: 33 · 2020: 29 · 2019: 24 · 2018: 30 · 2017: 40 · 2016: 24 · 2015: 45 · 2014: 38 · 2013: 36 · 2012: 46
- FWCI
- 14.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1385 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Hebrew University of Jerusalem
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Keywords
- retinal pigment epithelium, human embryonic stem cells, directed differentiation, nicotinamide, TGF-beta superfamily, neuronal differentiation, cell transplantation, retinal degeneration, age-related macular degeneration, retinitis pigmentosa, photoreceptor degeneration, stem cell therapy
- MeSH terms
- Animals, Cell Differentiation, Cell Line, Epithelial Cells, Flow Cytometry, Humans, Microscopy, Phase-Contrast, Immunophenotyping, Polymerase Chain Reaction, Transforming Growth Factor beta, Fibroblast Growth Factor 2, Cell Transplantation, Activins, Activin Receptors, Type I, Activin Receptors, Type II, Microscopy, Electron, Transmission, Rats, Embryonic Stem Cells, Retinal Pigment Epithelium
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review