J Korean Diabetes Assoc.  2005 Mar;29(2):103-111.

Induction of Tolerance to Complete Histocompatibility Mismatched Mice Islets through the Co-transplantation of Bone Marrow Cells in a Minimal Nonmyeloablative Condition

• Lee JI
• Oh SH
• Ahn YR
• Chae HY
• Lee BW
• Chung JH
• Min YK
• Lee MS
• Lee MK
• Kim KW

Abstract

BACKGROUND: Islet transplantation(IT) is a therapeutic approach that is used to prevent the dreaded diabetes complications that occur in those patients having an insulin deficient state. However, the requirement of undergoing a lifelong immunosuppressive regimen, along with the related side effects, to prevent rejection of the graft restricts this from being the preferred treatment for type 1 diabetes. One of the strategies to overcome these limitations is to induce tolerance induction and graft acceptance through the process of hematopoietic chimerism. In this study we investigated whether tolerance to MHC-disparate and minor-disparate islet allografts could be induced by the simultaneous transplantation of islets and bone marrow cells(BMCs) under a minimal nonmyeloablative conditioning state.
METHODS
The donor and recipient mice are BALB/c(H-2b) and C57BL/6(H-2d) mice, respectively. The streptozotocin induced diabetic C57BL/6(H-2d) mice received only 500 islets from the BALB/c(H-2b) mice in group 1. The group 2 recipients were conditioned with anti- lymphocyte serum(ALS), and 100cGy total body irradiation(TBI), and they were given islet cells of the BALB/c(H-2b) mice, but the group 3 mice were simultaneously given 30x106 BALB/c(H-2b) mice BMCs and islet cells in same condition as group 2. The chimerism of donor derived cells was analyzed by flow cytometry(FACS). Daily monitoring of blood glucose and immunohistochemical staining of the transplanted islets were used to assess the islet graft rejection and the islets' function.
RESULTS
We obtained 5~6% allogeneic donor chimerism and 60% of the grafts survived at 80 days after islet transplantation, Additionally, we found infiltration of lymphocytes around the islet without destruction of the endocrine cells, and the presence of vivid insulin/ glucagon stained-cells was detected in group 3.
CONCLUSION
This minimal nonmyeloablative conditioning therapy induced the donor's chimerism and immune tolerance between the MHC- and minor-disparate(BALB/c-->C57BL/6) mice. Long-term islet graft survival was obtained through the co-transplantation of BMCs in the mouse model

Keyword

Diabetes Mellitus; Islet of Langerhans; Transplantation; Bone marrow cells; Chimerism; Immune tolerance

MeSH Terms

Allografts
Animals
Behavior Therapy
Blood Glucose
Bone Marrow Cells*
Bone Marrow*
Chimerism
Diabetes Complications
Diabetes Mellitus
Endocrine Cells
Glucagon
Graft Rejection
Graft Survival
Histocompatibility*
Humans
Immune Tolerance
Insulin
Islets of Langerhans
Islets of Langerhans Transplantation
Lymphocytes
Mice*
Streptozocin
Tissue Donors
Transplantation
Transplants
Blood Glucose
Glucagon
Insulin
Streptozocin