Evaluation of immunoisolated insulin-secreting beta TC6-F7 cells as a bioartificial pancreas.
OBJECTIVE
To evaluate the growth and insulin secretion from microencapsulated beta TC6-F7 cells in vitro and to assess the in vivo function of microencapsulated cells transplanted in rats with steptozotocin (STZ)-induced diabetes.


METHODS
Alginate-poly-L-lysine encapsulated beta TC6-F7 cells were exposed to glucose, isobutylmethylxanthine (IBMX) and glucagon-like peptide I (7-36 amide) in a static in vitro challenge. In vivo, 2.5-3.5 x 10(7) encapsulated cells were implanted into diabetic rats. Graft function was evaluated by monitoring blood glucose concentrations and by an intraperitoneal glucose tolerance test.


RESULTS
The cell density (number of cells per capsule) of cultured microencapsulated beta TC6-F7 cells increased almost 35-fold over a 55 day observation period to reach a plateau of approximately 3500 cells/capsule. While insulin secretion per capsule remained unchanged over the first 21 days of culture, a 7-fold increase was observed during the last 14 days of the 55 day observation period. Intraperitoneal transplantation of 3.5 x 10(7) encapsulated cells into diabetic rats resulted, within 24 hours, in reversal of hyperglycemia for up to 60 days. Post-transplantation blood glucose concentrations varied between 2 and 4 mM. Glucose clearance rates evaluated by an intraperitoneal glucose tolerance test at 30 days post-transplantation resulted in a markedly flat glucose clearance curve with blood glucose never rising above 4 mM. The glucose challenge of microencapsulated cells recovered 30 days post-transplantation resulted in a 2-fold increase in insulin response at glucose concentrations greater than 5.5 mM as compared to glucose-free media. In addition, immunostaining of recovered grafted tissue for insulin, reveals a strong presence of the peptide within the cell population.


CONCLUSIONS
These data demonstrate the potential use of an immunoisolated beta-cell line for the treatment of diabetes.
Mamujee
S N
SN
Department of Physiology, Faculty of Medicine, University of Toronto, Ontario, Canada.
Zhou
D
D
Wheeler
M B
MB
Vacek
I
I
Sun
A M
AM
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002214:Capsules; D002455:Cell Division; D002469:Cell Separation / Q000379:methods; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000601:surgery*; D005934:Glucagon / Q000494:pharmacology; D052216:Glucagon-Like Peptide 1; D005951:Glucose Tolerance Test; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007340:Insulinoma / Q000378:metabolism*; D019397:Pancreas, Artificial; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D011498:Protein Precursors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014407:Tumor Cells, Cultured
D001786:Blood Glucose; D002214:Capsules; D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D015056:1-Methyl-3-isobutylxanthine