Abstract | BACKGROUND: Cellular replacement therapy represents a promising strategy for treating type I diabetes; however, such an approach is limited due to the inadequate availability of human donor tissue. Here we investigated the extent to which human islet tissue can be expanded in monolayer culture and brought back to islet function. METHODS: RESULTS: The cultured monolayer cells secreted insulin in response to glucose stimulation and maintained endocrine gene expression. Encapsulated islet-like clusters displayed cellular architecture similar to freshly isolated and encapsulated adult human islets maintained in culture, exhibiting an immunoreactive core of insulin, glucagon, and somatostatin, as well as peripheral cytokeratin-19 staining. Encapsulated aggregates significantly reduced hyperglycemia in transplanted mice within 1 week and normoglycemia was achieved after 5 weeks. Human C-peptide was detected in transplanted mice concomitant with the reduction in hyperglycemia. Capsules recovered 8 weeks posttransplantation exhibited insulin immunoreactivity. CONCLUSIONS: Collectively, these data indicate that adult human pancreatic islet cells can be expanded by three serial passages while maintaining their endocrine properties and can yield functional islet-like cell clusters through intracapsular aggregation that reverse hyperglycemia in diabetic mice. This culture and aggregation process could serve as a platform for proliferation and differentiation studies of endocrine lineage cells.
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Authors | Wen-Ghih Tsang, Tianli Zheng, Yanping Wang, Jinghua Tang, Howard B Rind, Aleksandar Francki, Nataliya Bufius |
Journal | Transplantation
(Transplantation)
Vol. 83
Issue 6
Pg. 685-93
(Mar 27 2007)
ISSN: 0041-1337 [Print] United States |
PMID | 17414699
(Publication Type: Journal Article)
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Chemical References |
- Blood Glucose
- C-Peptide
- Capsules
- Insulin
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Topics |
- Animals
- Blood Glucose
(metabolism)
- C-Peptide
(blood)
- Capsules
- Cell Aggregation
(physiology)
- Cell Culture Techniques
(methods)
- Cell Proliferation
- Cells, Cultured
- Diabetes Mellitus, Experimental
(blood, surgery)
- Humans
- Insulin
(metabolism)
- Islets of Langerhans
(cytology, metabolism)
- Islets of Langerhans Transplantation
(methods)
- Male
- Mice
- Mice, SCID
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