Amelioration of hyperglycemia in streptozotocin-induced diabetic mice with fetal pancreatic allografts: prevention of rejection by donor specific transfusion in conjunction with CTLA4Ig.
BACKGROUND
Fetal pancreas has been considered as an alternative donor source for islet transplantation since it has potent capacity for beta cell differentiation and proliferation. However, prevention of fetal pancreatic allograft rejection can be hardly achieved compared with adult islet allografts.


OBJECTIVE
The aim of the study is to determine whether donor specific transfusion (DST) in conjunction with CTLA4Ig has any favorable effect on prevention of fetal pancreatic allograft rejection in mice.


METHODS
BALB/c splenocytes (SPC, 1 x 10) were injected iv into C57BL/6 mice in conjunction with CTLA4Ig (ip, 50 microgram, day 0, 2, and 4). Fourteen days later, the mice were made diabetic with streptozotocin (STZ, iv) and donor specific or third party pancreatic allografts were transplanted beneath the kidney capsule.


RESULTS
Morphologically, it was found that rejection of fetal pancreatic allografts can be prevented at 30 days after transplantation only when donor specific allografts were grafted into the mice treated with DST in conjunction with CTLA4Ig. Functionally, 3 out of 9 diabetic mice became normoglycemic by 120 days after transplantation of fetal pancreatic allografts.


CONCLUSIONS
DST in conjunction with CTLA4Ig can have a favorable effect on prevention of fetal pancreatic allograft rejection resulting in amelioration of STZ-induced diabetes in mice.
Hirakawa
Eiji
E
Departments of Surgery I, Fukuoka University School of Medicine, Fukuoka 814-0180, Japan.
Yasunami
Yohichi
Y
Nakano
Masahiko
M
Shiiba
Masafumi
M
Takehara
Megumi
M
Uede
Toshimitsu
T
Todo
Satoru
S
Ono
Junko
J
Ikeda
Seiyo
S
D000069594:Abatacept; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003131:Combined Modality Therapy; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy / Q000628:therapy*; D016332:Fetal Tissue Transplantation / Q000473:pathology; D005951:Glucose Tolerance Test; D006084:Graft Rejection / Q000517:prevention & control*; D018796:Immunoconjugates / Q000627:therapeutic use*; D051379:Mice; D016035:Pancreas Transplantation / Q000473:pathology
D001786:Blood Glucose; D018796:Immunoconjugates; D000069594:Abatacept