Rat islet cell aggregates are superior to islets for transplantation in microcapsules.
OBJECTIVE
Islet transplantation is a promising treatment for type 1 diabetes but is hampered by a shortage of donor human tissue and early failure. Research on islet cell transplantation includes finding new sources of cells and immunoisolation to protect from immune assault and tumourigenic potential. Small islet cell aggregates were studied to determine if their survival and function were superior to intact islets within microcapsules because of reduced oxygen transport limitation and inflammatory mediators.


METHODS
Islet cell aggregates were generated by dispersing rat islets into single cells and allowing them to re-aggregate in culture. Rat islets and islet cell aggregates were encapsulated in barium alginate capsules and studied when cultured in low (0.5% or 2%) or normal (20%) oxygen, or transplanted into mice.


RESULTS
Encapsulated islet cell aggregates were able to survive and function better than intact islets in terms of oxygen-consumption rate, nuclei counts, insulin-to-DNA ratio and glucose-stimulated insulin secretion. They also had reduced expression of pro-inflammatory genes. Islet cell aggregates showed reduced tissue necrosis in an immunodeficient transplant model and a much greater proportion of diabetic xenogeneic transplant recipients receiving islet cell aggregates (tissue volume of only 85 islet equivalents) had reversal of hyperglycaemia than recipients receiving intact islets.


CONCLUSIONS
These aggregates were superior to intact islets in terms of survival and function in low-oxygen culture and during transplantation and are likely to provide more efficient utilisation of islet tissue, a finding of importance for the future of cell therapy for diabetes.
O'Sullivan
E S
ES
Section on Islet Transplantation and Cell Biology, Research Division, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, USA.|Department of Medicine, Harvard Medical School, Boston, MA, USA.
Johnson
A S
AS
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Omer
A
A
Section on Islet Transplantation and Cell Biology, Research Division, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, USA.|Department of Medicine, Harvard Medical School, Boston, MA, USA.
Hollister-Lock
J
J
Section on Islet Transplantation and Cell Biology, Research Division, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, USA.
Bonner-Weir
S
S
Section on Islet Transplantation and Cell Biology, Research Division, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, USA.|Department of Medicine, Harvard Medical School, Boston, MA, USA.
Colton
C K
CK
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Weir
G C
GC
Section on Islet Transplantation and Cell Biology, Research Division, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, USA.|Department of Medicine, Harvard Medical School, Boston, MA, USA.
D000704:Analysis of Variance; D000818:Animals; D002214:Capsules / Q000378:metabolism; D002449:Cell Aggregation; D002452:Cell Count; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000601:surgery*; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014183:Transplantation, Heterologous
D002214:Capsules