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Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocin-induced diabetic mice.
Abstract
Embryonic stem (ES) cells display the ability to differentiate in vitro into a variety of cell lineages. Using a cell-trapping system, we have obtained an insulin-secreting cell clone from undifferentiated ES cells. The construction used allows the expression of a neomycin selection system under the control of the regulatory regions of the human insulin gene. The chimeric gene also contained a hygromycin resistance gene (pGK-hygro) to select transfected cells. A resulting clone (IB/3x-99) containing 16.5 ng/microg protein of total insulin displays regulated hormone secretion in vitro in the presence of various secretagogues. Clusters obtained from this clone were implanted (1 x 10(6) cells) in the spleen of streptozotocin-induced diabetic animals. Transplanted animals correct hyperglycemia within 1 week and restore body weight in 4 weeks. Whereas an intraperitoneal glucose tolerance test showed a slower recovery in transplanted versus control mice, blood glucose normalization after a challenge meal was similar. This approach opens new possibilities for tissue transplantation in the treatment of type 1 and type 2 diabetes and offers an alternative to gene therapy.
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Citations
Cited by
Differentiation of Embryonic Stem Cells to Insulin-Secreting Structures Similar to Pancreatic Islets
Lumelsky, N., Blondel, O., Laeng, P., Velasco, I., Ravin, R., & McKay, R. (2001) · Science · doi:10.1126/science.1058866 · Cited by 1,453
Multilineage differentiation from human embryonic stem cell lines
Odorico, J. S., Kaufman, D. S., & Thomson, J. A. (2001) · Stem Cells · doi:10.1634/stemcells.19-3-193 · Cited by 969
Nistor, G. I., Totoiu, M. O., Haque, N., Carpenter, M. K., & Keirstead, H. S. (2005) · Glia · doi:10.1002/glia.20127 · Cited by 580
Pera, M. F., Reubinoff, B., & Trounson, A. (2000) · Journal of Cell Science · doi:10.1242/jcs.113.1.5 · Cited by 554
Duan, F. F., Liu, J. H., & March, J. C. (2015) · Diabetes · doi:10.2337/db14-0635 · Cited by 263
Metadata
- Authors
- Soria, B., Roche, E., Berná, G., León-Quinto, T., Reig, J. A., & Martín, F.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2000-02-01
- Volume
- 49
- Issue
- 2
- Pages
- 157-162
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2098338322
- Cited by
- 862
- References
- 0
- FWCI
- 61.80
- Type
- journal article
- Language
- en
- Open access
- closed
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- Soria, B., Roche, E., Berná, G., León-Quinto, T., Reig, J. A., & Martín, F. (2000). Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocin-induced diabetic mice. Diabetes. https://doi.org/10.2337/diabetes.49.2.157
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