Immune responses to an encapsulated allogeneic islet beta-cell line in diabetic NOD mice.
Our goal is to develop effective islet grafts for treating type 1 diabetes. Since human islets are scarce, we evaluated the efficacy of a microencapsulated insulin-secreting conditionally transformed allogeneic beta-cell line (betaTC-tet) in non-obese diabetic mice treated with tetracycline to inhibit cell growth. Relatively low serum levels of tetracycline controlled proliferation of betaTC-tet cells without inhibiting effective control of hyperglycemia in recipients. There was no significant host cellular reaction to the allografts or host cell adherence to microcapsules, and host cytokine levels were similar to those of sham-operated controls. We conclude that encapsulated allogeneic beta-cell lines may be clinically relevant, because they effectively restore euglycemia and do not elicit a strong cellular immune response following transplantation. To our knowledge, this is the first extensive characterization of the kinetics of host cellular and cytokine responses to an encapsulated islet cell line in an animal model of type 1 diabetes.
Black
Sasha P
SP
Charles River Laboratories, Pre-clinical Services Montreal, Senneville, Que., Canada H9X 3R3. Sasha.Black@ca.crl.com
Constantinidis
Ioannis
I
Cui
Hong
H
Tucker-Burden
Carol
C
Weber
Collin J
CJ
Safley
Susan A
SA
D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D002460:Cell Line; D016207:Cytokines / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology / Q000601:surgery*; D006087:Graft vs Host Reaction / Q000276:immunology*; D016381:Islets of Langerhans Transplantation / Q000276:immunology* / Q000379:methods*; D051379:Mice
D016207:Cytokines