Rapid and efficient directed differentiation of human pluripotent stem cells into retinal pigmented epithelium
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Controlling the differentiation of human pluripotent stem cells is the goal of many laboratories, both to study normal human development and to generate cells for transplantation. One important cell type under investigation is the retinal pigmented epithelium (RPE). Age-related macular degeneration (AMD), the leading cause of blindness in the Western world, is caused by dysfunction and death of the RPE. Currently, RPE derived from human embryonic stem cells are in clinical trials for the treatment of AMD. Although protocols to generate RPE from human pluripotent stem cells have become more efficient since the first report in 2004, they are still time-consuming and relatively inefficient. We have found that the addition of defined factors at specific times leads to conversion of approximately 80% of the cells to an RPE phenotype in only 14 days. This protocol should be useful for rapidly generating RPE for transplantation as well as for studying RPE development in vitro.
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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 Buchholz et al., 2013
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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
A ROCK inhibitor permits survival of dissociated human embryonic stem cells
Watanabe, K., Ueno, M., Kamiya, D., Nishiyama, A., Matsumura, M., Wataya, T., Takahashi, J. B., Nishikawa, S., Nishikawa, S.-I., Muguruma, K., et al. (2007) · Nature Biotechnology · doi:10.1038/nbt1310 · Cited by 2,055 · see citing works
Self-organizing optic-cup morphogenesis in three-dimensional culture
Eiraku, M., Takata, N., Ishibashi, H., Kawada, M., Sakakura, E., Okuda, S., Sekiguchi, K., Adachi, T., & Sasai, Y. (2011) · Nature · doi:10.1038/nature09941 · Cited by 2,001 · see citing works
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
Embryonic stem cell trials for macular degeneration: a preliminary report
Schwartz, S. D., Hubschman, J.-P., Heilwell, G., Franco-Cardenas, V., Pan, C. K., Ostrick, R. M., Mickunas, E., Gay, R., Klimanskaya, I., & Lanza, R. (2012) · The Lancet · doi:10.1016/s0140-6736(12)60028-2 · Cited by 1,409 · see citing works
Activin/Nodal and FGF pathways cooperate to maintain pluripotency of human embryonic stem cells
Vallier, L., Alexander, M., & Pedersen, R. A. (2005) · Journal of Cell Science · doi:10.1242/jcs.02553 · Cited by 948 · see citing works
Anderson, D. H., Radeke, M. J., Gallo, N. B., Chapin, E. A., Johnson, P. T., Curletti, C. R., Hancox, L. S., Hu, J., Ebright, J. N., Malek, G., et al. (2010) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2009.11.003 · Cited by 727 · see citing works
ROCK Inhibitor and Feeder Cells Induce the Conditional Reprogramming of Epithelial Cells
Liu, X., Ory, V., Chapman, S., Yuan, H., Albanese, C., Kallakury, B., Timofeeva, O. A., Nealon, C., Dakic, A., Simic, V., et al. (2012) · The American Journal of Pathology · doi:10.1016/j.ajpath.2011.10.036 · Cited by 726 · see citing works
Efficient generation of retinal progenitor cells from human embryonic stem cells
Lamba, D. A., Karl, M., Ware, C. B., & Reh, T. A. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601990103 · Cited by 691 · see citing works
Gene expression patterns in human embryonic stem cells and human pluripotent germ cell tumors
Sperger, J. M., Chen, X., Draper, J. S., Antosiewicz, J. E., Chon, C. H., Jones, S. B., Brooks, J. D., Andrews, P. W., Brown, P. O., & Thomson, J. A. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2235735100 · Cited by 648 · see citing works
Modeling early retinal development with human embryonic and induced pluripotent stem cells
Meyer, J. S., Shearer, R., Capowski, E., Wright, L., Wallace, K., Mcmillan, E., Zhang, S.-C., & Gamm, D. (2009) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0905245106 · Cited by 609 · see citing works
Specification of the vertebrate eye by a network of eye field transcription factors
Zuber, M. E., Gestri, G., Viczian, A. S., Barsacchi, G., & Harris, W. A. (2003) · Development · doi:10.1242/dev.00723 · Cited by 541 · see citing works
Activin A Maintains Pluripotency of Human Embryonic Stem Cells in the Absence of Feeder Layers
Beattie, G. M., Lopez, A. D., Bucay, N., Hinton, A. C., Firpo, M. T., King, C. C., & Hayek, A. (2005) · Stem Cells · doi:10.1634/stemcells.2004-0279 · Cited by 503 · see citing works
Idelson, M., Alper, R., Obolensky, A., Ben-Shushan, E., Hemo, I., Yachimovich-Cohen, N., Khaner, H., Smith, Y., Wiser, O., Gropp, M., et al. (2009) · Cell stem cell · doi:10.1016/j.stem.2009.07.002 · Cited by 486 · 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
Derivation of functional retinal pigmented epithelium from induced pluripotent stem cells
Buchholz, D. E., Hikita, S. T., Rowland, T. J., Friedrich, A. M., Hinman, C. R., Johnson, L. V., & Clegg, D. O. (2009) · Stem Cells · doi:10.1002/stem.189 · Cited by 417 · see citing works
Self-citationCarr, 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
Self-citationXiao, L., Yuan, X., & Sharkis, S. J. (2006) · Stem Cells · doi:10.1634/stemcells.2005-0299 · Cited by 354 · see citing works
Human keratinocytes are efficiently immortalized by a Rho kinase inhibitor
Chapman, S., Liu, X., Meyers, C., Schlegel, R., & McBride, A. A. (2010) · Journal of Clinical Investigation · doi:10.1172/jci42297 · Cited by 314 · 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
Okumura, N., Koizumi, N., Ueno, M., et al. (2012) · American Journal Of Pathology · doi:10.1016/j.ajpath.2012.03.033 · Cited by 264 · see citing works
Neural and Head Induction by Insulin-like Growth Factor Signals
Pera, E. M., Wessely, O., Li, S.-Y., & Robertis, E. M. D. (2001) · Developmental Cell · doi:10.1016/s1534-5807(01)00069-7 · Cited by 229 · see citing works
Hu, Y., Liu, L., Lü, B., et al. (2012) · Ophthalmic Research · doi:10.1159/000338749 · Cited by 123 · see citing works
Ahmado, A., Carr, A.-J., Vugler, A. A., Semo, M., Gias, C., Lawrence, J. M., Chen, L. L., Chen, F. K., Turowski, P., da Cruz, L., et al. (2011) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.10-6374 · Cited by 100 · see citing works
Self-citationAge-Related Macular Degeneration
Khandhadia, S., Cherry, J., & Lotery, A. J. (2012) · Advances in experimental medicine and biology · doi:10.1007/978-1-4614-0653-2_2 · Cited by 97 · 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
Self-citationLin, H., & Clegg, D. (1998) · PubMed · Cited by 77 · see citing works
Self-citationZahabi, 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
Lonely death dance of human pluripotent stem cells: ROCKing between metastable cell states
Ohgushi, M., & Sasai, Y. (2011) · Trends in Cell Biology · doi:10.1016/j.tcb.2011.02.004 · Cited by 74 · 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
Radeke, M. J., Peterson, K. E., Johnson, L. V., & Anderson, D. H. (2007) · Experimental Eye Research · doi:10.1016/j.exer.2007.05.006 · Cited by 60 · see citing works
Nicotinamide induces differentiation of embryonic stem cells into insulin-secreting cells
Vaca, P., Berná, G., Legido, R. A., et al. (2007) · Experimental Cell Research · doi:10.1016/j.yexcr.2007.11.019 · Cited by 60 · see citing works
Chen, F. K., Uppal, G., MacLaren, R. E., Coffey, P. J., Rubin, G. S., Tufail, A., Aylward, G. W., & da Cruz, L. (2008) · Clinical and Experimental Ophthalmology · doi:10.1111/j.1442-9071.2009.01915.x · Cited by 52 · see citing works
Self-citationChen, F. K., Patel, P. J., Uppal, G., Rubin, G. S., Coffey, P. J., Aylward, G. W., & da Cruz, L. (2009) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.08-2845 · Cited by 38 · see citing works
Self-citationNicotinamide 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
Chen, F. K., Patel, P. J., Uppal, G., Tufail, A., Coffey, P. J., & da Cruz, L. (2010) · British Journal of Ophthalmology · doi:10.1136/bjo.2009.172593 · Cited by 30 · see citing works
Self-citationCanadian expert consensus: optimal treatment of neovascular age-related macular degeneration
Cruess, A. F., Berger, A. R., Colleaux, K. M., Greve, M. D. J., Harvey, P. T., Kertes, P. J., Sheidow, T., Tourville, É., Williams, G., & Wong, D. T. (2012) · Canadian Journal of Ophthalmology · doi:10.1016/j.jcjo.2012.03.007 · Cited by 27 · see citing works
Identification of Leptospira biflexa by real-time homogeneous detection of rapid cycle PCR product
Woo, T. H. S., Patel, B. K. C., Cinco, M., et al. (1999) · Journal of Microbiological Methods · doi:10.1016/s0167-7012(98)00095-5 · Cited by 25 · see citing works
Koh, S. M. (2000) · Progress in Retinal and Eye Research · doi:10.1016/s1350-9462(00)00010-0 · Cited by 22 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- Woo TH, Patel BK, Cinco M et al. Identi- fication of Leptospira biflexa by real-time ho- mogeneous detection of rapid cycle PCR prod- uct. J Microbiol Methods 1999;35:23-30.
- Beattie GM, Lopez AD, Bucay N et al. Ac- tivin A maintains pluripotency of human em- bryonic stem cells in the absence of feeder lay- ers. STEM CELLS 2005;23:489 -495.
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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
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
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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
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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
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
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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
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
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Vu, T. Q., de Castro, R. M. B., & Qin, L. (2017) · Lab on a Chip · doi:10.1039/c6lc01367h · Cited by 63 · see citing works
Müller, C., Charniga, C., Temple, S., & Finnemann, S. C. (2018) · Stem Cell Reports · doi:10.1016/j.stemcr.2018.01.017 · Cited by 61 · see citing works
Parikh, B. H., Liu, Z., Blakeley, P., Lin, Q., Singh, M., Ong, J. Y., Ho, K. H., Lai, J. W., Bogireddi, H., Tran, K. C., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-30474-6 · Cited by 54 · see citing works
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Truong, V., Viken, K., Geng, Z., Barkan, S., Johnson, B., Ebeling, M. C., Montezuma, S. R., Ferrington, D. A., & Dutton, J. R. (2021) · SLAS TECHNOLOGY · doi:10.1177/2472630320972110 · Cited by 30 · see citing works
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Self-citation
- Authors
- Buchholz, D. E., Pennington, B. O., Croze, R. H., Hinman, C. R., Coffey, P. J., & Clegg, D. O.
- Affiliations
- University of California, Santa Barbara (US)
- Corresponding author
- Coffey, Peter J.
- Clegg, Dennis O.
- Venue
- Stem Cells Translational Medicine
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-04-18
- Volume
- 2
- Issue
- 5
- Pages
- 384-393
- ISSN
- 2157-6564 (ISSN-L)
- 2157-6580
- PMC
- PMC3667566
- OpenAlex
- W1987713800
- Cited by
- 261
- References
- 39
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 10 · 2023: 14 · 2022: 23 · 2021: 30 · 2020: 24 · 2019: 18 · 2018: 26 · 2017: 25 · 2016: 18 · 2015: 30 · 2014: 22 · 2013: 9
- FWCI
- 11.79
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Stem Cells Translational Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- California Institute for Regenerative Medicine (CL1-00521, DR1-01444, FA1-006161, TG2-01151)
- Institute for Collaborative Biotechnologies (W911NF-09-0001)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Keywords
- retinal pigment epithelium, human pluripotent stem cells, directed differentiation, age-related macular degeneration, cell transplantation, embryonic stem cells
- MeSH terms
- Cell Differentiation, Cell Line, Cells, Cultured, Gene Expression Regulation, Humans, Niacinamide, Pyrroles, RNA, Messenger, Time Factors, Vasoactive Intestinal Peptide, Visual Fields, Cell Lineage, Activins, Pluripotent Stem Cells, Cell Proliferation, Retinal Pigment Epithelium
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