J Korean Diabetes Assoc.  2006 Jan;30(1):54-63.

The effects of mixed chimerism conducted by natural killer cell depletion with non myeloablation on islet allograft rejection

• Park HS
• Cho SG
• Park CG
• Hong OK
• Kim JW
• Kim BR
• Yoon KH

Abstract

BACKGROUND: Because of the shortage of human pancreas and immunorejection, very small fraction of patients with type 1 diabetes can be treated with islet transplantation. The immune tolerance induction for overcoming the immume rejectin of trausplamted islets could be conducted by hematopoietic mixed chimerims with various invasive methods. The purpose of this study is to investigate the effect of mixed chimerims conducted by newly developed minimally invasive methods on islet allografts rejection in streptozotocin induced diabetic mice.
METHODS
Recipient, Balb/c(H-2Kd) mice were injected intraperitoneally with anti- asialoGM1 antibody at one day before bone marrow transplantation. There were received total body irradiation at a dose of 500 cGy and followed by tail vein injection of the 2 x 10(7) T-cell depleted bone marrow cells from C57BL/6(H-2Kb). Mixed chimerism mice were determined by gDNA PCR of lymphocyte MHC class I gene (H-2K) on 21st day. Streptozotocin induced diabetic mixed chimera mice were received islet transplantation from bone marrow donors. Grafts, spleen and peripheral blood were obtained from the mixed chimera mice, and there were used by Immunohistochimeical staining, flow cytometric analysis and gDNA PCR on 21st day.
RESULTS
The blood glucose levels of streptozotocin induced diabetic mice were normalized by transplantation of bone marrow donor islets and maintained during 30 days. After removal of first islet allografts, hyperglycemia was re-established. We could re-confirmed donor specific tolerance of transplanted islets by second transplantation of bone marrow donor islets. Normoglycemia was maintained during 21 days after second islet transplantation. Furthermore islet grafts from MHC-mismatched third party mice were immediately rejected. Flow cytometric analysis results suggest that the mixed chimerism mice were maintain during the whole study period.
CONCLUSION
The mixed chimerism model conducted by newly developed and minimally invasive method effectively prevents the islet allo grafts rejection in STZ-induced mixed chimerism mice.

Keyword

Insulin; Islet; Transplantation; Mixed chimera; Type 1 diabete

MeSH Terms

Allografts*
Animals
Blood Glucose
Bone Marrow
Bone Marrow Cells
Bone Marrow Transplantation
Chimera
Chimerism*
Genes, MHC Class I
Humans
Hyperglycemia
Immune Tolerance
Insulin
Islets of Langerhans Transplantation
Killer Cells, Natural*
Lymphocytes
Mice
Pancreas
Polymerase Chain Reaction
Spleen
Streptozocin
T-Lymphocytes
Tissue Donors
Transplantation
Transplants
Veins
Whole-Body Irradiation
Blood Glucose
Insulin
Streptozocin

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