The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
A genetically engineered human pancreatic β cell line exhibiting glucose-inducible insulin secretion
Open accessAbstract
Despite intense efforts over the past 30 years, human pancreatic β cell lines have not been available. Here, we describe a robust technology for producing a functional human β cell line using targeted oncogenesis in human fetal tissue. Human fetal pancreatic buds were transduced with a lentiviral vector that expressed SV40LT under the control of the insulin promoter. The transduced buds were then grafted into SCID mice so that they could develop into mature pancreatic tissue. Upon differentiation, the newly formed SV40LT-expressing β cells proliferated and formed insulinomas. The resulting β cells were then transduced with human telomerase reverse transcriptase (hTERT), grafted into other SCID mice, and finally expanded in vitro to generate cell lines. One of these cell lines, EndoC-βH1, expressed many β cell-specific markers without any substantial expression of markers of other pancreatic cell types. The cells secreted insulin when stimulated by glucose or other insulin secretagogues, and cell transplantation reversed chemically induced diabetes in mice. These cells represent a unique tool for large-scale drug discovery and provide a preclinical model for cell replacement therapy in diabetes. This technology could be generalized to generate other human cell lines when the cell type-specific promoter is available.
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Cites
Multiply attenuated lentiviral vector achieves efficient gene delivery in vivo
Zufferey, R., Nagy, D., Mandel, R. J., Naldini, L., & Trono, D. (1997) · Nature Biotechnology · doi:10.1038/nbt0997-871 · Cited by 1,977
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Human and rat beta cells differ in glucose transporter but not in glucokinase gene expression.
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Proliferation of sorted human and rat beta cells
Parnaud, G., Bosco, D., Berney, T., Pattou, F., Kerr-Conte, J., Donath, M. Y., Bruun, C., Mandrup-Poulsen, T., Billestrup, N., & Halban, P. A. (2007) · Diabetologia · doi:10.1007/s00125-007-0855-1 · Cited by 232
Cited by
Mahajan, A., Spracklen, C. N., Zhang, W., Ng, M. C. Y., Petty, L. E., Kitajima, H., Yu, G. Z., Rüeger, S., Speidel, L., Kim, Y. J., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01058-3 · Cited by 704
Physiological roles of hydrogen sulfide in mammalian cells, tissues, and organs
Cirino, G., Szabo, C., & Papapetropoulos, A. (2023) · Physiological Reviews · doi:10.1152/physrev.00028.2021 · Cited by 553
Metabolic Signaling in Fuel-Induced Insulin Secretion
Prentki, M., Matschinsky, F. M., & Madiraju, S. R. M. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.05.018 · Cited by 548
Morán, I., Akerman, İ., van de Bunt, M., Xie, R., Benazra, M., Nammo, T., Arnes, L., Nakić, N., García-Hurtado, J., Rodríguez-Seguí, S., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.08.010 · Cited by 447
Self-citationthe DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Gaulton, K. J., Ferreira, T., Lee, Y., Raimondo, A., Mägi, R., Reschen, M. E., Mahajan, A., Locke, A., William Rayner, N., et al. (2015) · Nature Genetics · doi:10.1038/ng.3437 · Cited by 398
Metadata
- Authors
- Ravassard, P., Hazhouz, Y., Pechberty, S., Bricout-Neveu, E., Armanet, M., Czernichow, P., & Scharfmann, R.
- Venue
- Journal of Clinical Investigation
- Published
- 2011-09-01
- Volume
- 121
- Issue
- 9
- Pages
- 3589-3597
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2055492712
- Cited by
- 576
- References
- 4
- FWCI
- 20.49
- Type
- journal article
- Language
- en
- Open access
- green
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- Ravassard, P., Hazhouz, Y., Pechberty, S., Bricout-Neveu, E., Armanet, M., Czernichow, P., & Scharfmann, R. (2011). A genetically engineered human pancreatic β cell line exhibiting glucose-inducible insulin secretion. Journal of Clinical Investigation. https://doi.org/10.1172/jci58447
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