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Am J Physiol Cell Physiol 274: C1356-C1362, 1998;
0363-6143/98 $5.00
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Vol. 274, Issue 5, C1356-C1362, May 1998

In vitro and in vivo evaluation of insulin-producing beta TC6-F7 cells in microcapsules

D. Zhou1, A. M. Sun1, X. Li1,2, S. N. Mamujee1, I. Vacek1, J. Georgiou1, and M. B. Wheeler1,2

Departments of 1 Physiology and 2 Medicine, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada M5S 1A8

In the present study, the insulin secretory capacity of beta TC6-F7 cells in microcapsules was evaluated. The cell mass within capsules was found to expand in a three-dimensional fashion, in contrast to cells seeded on plates that grew as a monolayer. In in vitro studies, both free and encapsulated cells were found to secrete insulin in the absence of glucose, at 13.6 ± 1.1 and 14.5 ± 0.9 ng · 106 cells-1 · 60 min-1, respectively, with the response rising to a maximum of 26.0 ± 0.8 and 31 ± 2.3 ng · 106 cells-1 · 60 min-1 in the presence of 16.8 mM glucose. Encapsulated cells were able to produce Ca2+ responses in the presence of KCl (50 mM) and BAY K 8644 (100 µM). In in vivo studies, intraperitoneal transplantation of 3.0 ×106 microencapsulated cells into mice (n = 5) with streptozotocin-induced diabetes resulted in the restoration of normoglycemia up to 57 days. Insulin concentrations rose from 0.4 ± 0.1 ng/ml before the graft administration to 2.2 ± 0.8 ng/ml after the transplantation in the normoglycemic recipients. An oral glucose challenge in transplant recipients demonstrated a flat glucose response, suggesting extremely high glucose clearance rates. These data demonstrate the potential use of the immunoisolated beta -cell lines for the treatment of diabetes.

insulin-producing cells; microencapsulation; xenografts; transplantation





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