Effect of Immunorejection after Transplantation of Bone Marrow Donor’s Islets in Streptozotocin-Induced Diabetes Mellitus Hematopoietic Mixed Chimerism Mouse Model
Heon-seok Park, Seok-goo Cho, Jung-gyu Park, Oak-kee Hong, Ji-won Kim, Bo-ryung Kim, Kun-ho Yoon
Affiliation : Division of Endocrinology and Metabolism, Department of Internal Medicine, The Catholic University of Korea, Kangnam St. Mary’s Hospital, Seoul, Repulic of korea(south korea)
Background and Aims. The current success with islet allograft transplantation is reviewed however the
shortage of human islet tissue and immune rejection mean that only a small fraction of people with diabetes
would be able to benefit. The immune tolerance induction conducted by hematopoietic mixed chimerism with
minimal invasive methods may be the ideal alternative to overcome not only immune rejection also the
toxicities of immunosuppressive drugs. The purpose of this study is to investigate the effect of mixed chimerism
conducted by newly developed minimally invasive methods on islet allografts rejection in streptozotocin
induced diabetic mice.
Materials and Methods. Recipient. Balb/c(H-2Kd) mouse was injected intraperitoneally with anti-asialoGM1
antibody on day -1 before bone marrow transplantation. It received total body irradiation at a dose of 500
cGy and followed by tail vein injection of the 2x107 T-cell depleted bone marrow cells from C57BL/6(H-2Kb).
Mixed chimerism mouse determined by gDNA PCR of lymphocyte MHC class I gene (H-2K) on day 21.
Streptozotocin induced diabetic mixed chimera mouse was received islet transplantation from bone marrow
donors. Grafts and spleen, peripheral blood were obtained from the mixed chimera mouse and there were by
use of Immunohistochimerstry stain, flow cytometric analysis and gDNA PCR on day 21.
Results. The blood glucose level was normalized by transplantation of bone marrow donor‘s islets and
maintained during 21 days. After removal of first islet allo-grafts, diabetes mellitus was re-established. We
could confirmed donor specific tolerance of transplanted islets by second transplantation of bone marrow
donor‘s islets. Normoglycemia was maintained for 21 days after second islet transplantation. Furthermore
islet graft from mismatched third party mouse were immediately rejected. Flow cytometric analysis results
suggest that T-cell depleted bone marrow induced mixed chimerism mice was maintain during the whole study
period.
Conclusion. The mixed chimerism conducted by newly developed minimally invasive methods effectively
prevent the islet allografts rejection in streptozotocin induced diabetic mice.
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