Assessment of insulin secretion in vitro from microencapsulated fetal porcine islet-like cell clusters and rat, mouse, and human pancreatic islets.
BACKGROUND
The possibility of transplanting microencapsulated pancreatic islets into patients with insulin-dependent diabetes mellitus, either as allografts or xenografts, has attracted great interest. A critical evaluation of the results obtained reveals that the success has been very limited. The aim of the present study was to compare the in vitro function of microencapsulated islets obtained from adult humans, adult mice, adult rats, and fetal pigs.


METHODS
Human pancreatic islets were isolated at beta-Cell Transplant in Brussels, Belgium, and sent to the Department of Medical Cell Biology, Uppsala University in Uppsala, Sweden. Rat and mouse pancreatic islets and fetal porcine islet-like cell clusters (ICC) were prepared in Uppsala. All groups of islets were subsequently sent to the Department of Biotechnology, Norwegian Institute of Biotechnology, University of Trondheim, Trondheim, Norway. After 1 day in tissue culture, the islets were microencapsulated in alginate then cultured and sent back to Uppsala the next day. After either overnight culture (day 1) or 6 days of culture (day 6), the microencapsulated islets were examined for their insulin content and insulin release. Nonencapsulated islets from the same isolations were used as controls.


RESULTS
The insulin content of rodent and human islets was not affected by microencapsulation, whereas porcine ICC showed a diminished insulin content. Microencapsulated porcine ICC also had a marked reduction in their insulin secretion in response to stimulation with glucose or glucose + theophylline both on days 1 and 6 in tissue culture. Mouse islets showed a reduced insulin response at both time points. Rat islets exhibited an inhibition of insulin secretion on day 1, but this had been restored by day 6. Human islets had well-preserved insulin secretion after both days 1 and 6. Microencapsulated human islets showed a normal morphology 3-4 weeks after intraperitoneal transplantation to nude mice.


CONCLUSIONS
Pancreatic islets isolated from human, rat, and mouse donors show a glucose-stimulated insulin release in vitro after microencapsulation and repeated transports between laboratories. The insulin secretory capacity of microencapsulated human and rat islets was preserved best, whereas mouse islets and particularly fetal porcine ICC were impaired by microencapsulation.
Sandler
S
S
Department of Medical Cell Biology, Uppsala University, Sweden.
Andersson
A
A
Eizirik
D L
DL
Hellerström
C
C
Espevik
T
T
Kulseng
B
B
Thu
B
B
Pipeleers
D G
DG
Skjåk-Braek
G
G
D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D004339:Drug Compounding; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D051381:Rats; D017207:Rats, Sprague-Dawley; D013552:Swine
D007328:Insulin