Reversal of diabetes by βTC3 cells encapsulated in alginate beads generated by emulsion and internal gelation.
Encapsulation of insulin-producing cells in alginate beads could improve the treatment of type 1 diabetes by reducing or eliminating the need for immunosuppression. We have recently adapted an emulsion and internal gelation process to β-cell encapsulation. This process has the advantages of being well suited for m(3)/h production rates and allowing the use of increased alginate concentrations. Compared with 1.5% alginate beads generated by a standard extrusion process, 5% alginate emulsion-generated beads demonstrated greater in vitro stability and greater volumetric exclusion of antibody-sized pullulan. When βTC3 cells were transplanted into streptozotocin-induced allogeneic diabetic mice, a significant decrease in the blood glucose levels was seen within 2 days with the 5% emulsion-generated beads but not until >16 days with the 1.5% extrusion-generated beads. This was correlated with higher cell survival and lower graft-specific plasma immunoglobulin levels. These results suggest that higher-concentration alginate beads generated by emulsion and internal gelation have improved graft immunoprotection. The emulsion process is a promising and scalable technology for cellular therapies requiring immune isolation.
Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada. corinne.hoesli@gmail.com
Corinne A
CA
Hoesli
Roger L J
RL
Kiang
Dušana
D
Mocinecová
Madeleine
M
Speck
Daniela Jochec
DJ
Mošková
Christine
C
Donald-Hague
Igor
I
Lacík
Timothy J
TJ
Kieffer
James M
JM
Piret
D000464:Alginates / Q000737:chemistry*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002470:Cell Survival; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D020285:Cryoelectron Microscopy / Q000379:methods; D003920:Diabetes Mellitus / Q000628:therapy*; D004655:Emulsions; D005782:Gels / Q000737:chemistry; D020100:Hydrogels / Q000737:chemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning / Q000379:methods; D010539:Permeability; D013314:Stress, Mechanical; D014184:Transplantation, Homologous / Q000379:methods; D014783:Viscosity
D000464:Alginates; D001786:Blood Glucose; D004655:Emulsions; D005782:Gels; D020100:Hydrogels; D007166:Immunosuppressive Agents; D007328:Insulin