In vitro and in vivo evaluation of insulin-producing beta TC6-F7 cells in microcapsules.
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.10(6) cells-1.60 min-1, respectively, with the response rising to a maximum of 26.0 +/- 0.8 and 31 +/- 2.3 ng.10(6) 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 microM). In in vivo studies, intraperitoneal transplantation of 3.0 x 10(6) 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.
Zhou
D
D
Department of Physiology, Faculty of Medicine, University of Toronto, Ontario, Canada.
Sun
A M
AM
Li
X
X
Mamujee
S N
SN
Vacek
I
I
Georgiou
J
J
Wheeler
M B
MB
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002118:Calcium / Q000378:metabolism; D002214:Capsules; D017690:Cell Transplantation; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000096:biosynthesis* / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D010537:Peritoneum / Q000601:surgery; D012016:Reference Values; D016042:Transplantation, Heterotopic; D014407:Tumor Cells, Cultured
D001786:Blood Glucose; D002214:Capsules; D007328:Insulin; D005947:Glucose; D002118:Calcium