A more persistent tolerance to islet allografts through bone marrow transplantation in minimal nonmyleoablative conditioning therapy

byungwan lee, J. I. Lee, S. H. Oh, Y. R. Ahn, H. Y. Chae, M. S. Lee, M. K. Lee, K. W. Kim

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Introduction. Islet transplantation is a therapeutic approach to prevent diabetes complications. However, the side effects of the required lifelong immunosuppressive regimens to prevent graft rejection restrict the impact of type 1 diabetes. One strategy to overcome these limitations is tolerance induction and graft acceptance through hematopoietic chimerism. In this study we investigated whether tolerance to major histocompability complex (MHC) and minor-disparate islet allografts could be induced by minimal nonmyeloablative conditioning and whether more persistent donor-specific islet allografts were accepted if the grafts were implanted with simultaneous bone marrow cells. Methods. The donor and recipient mice were BALB/c(H-2 b ) and C57BL/6(H-2 d ), respectively. In group 1 streptozotocin-induced diabetic C57BL/6(H-2 d ) mice received only 500 islets of BALB/c(H-2 b ). Group 2 recipients conditioned with antilymphocyte serum, 100 cGy total body irradiation and cyclophosphamide were given islet cells of BALB/c(H-2 b ), but group 3 were simultaneously given 30 × 10 6 BALB/c(H-2 b ) mice BMCs and islet cells similar to group 2. Results. We obtained 5% to 6% allogeneic donor chimerism and 60% graft survival at 80 days after islet transplantation in group 3. We observed lymphocyte infiltration around the islet without destruction of endocrine cells and the presence of strong insulin/glucagon-stained cells in group 3. Conclusion. This minimal nonmyeloablative conditioning therapy induced donor chimerism and immune tolerance between MHC- and minor-disparate (BALB/c→C57BL/6) mice and long-term islet graft survival was obtained through cotransplantation of bone marrow cells.

Original languageEnglish
Pages (from-to)2266-2269
Number of pages4
JournalTransplantation Proceedings
Volume37
Issue number5
DOIs
Publication statusPublished - 2005 Jun 1

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Behavior Therapy
Bone Marrow Transplantation
Chimerism
Allografts
Islets of Langerhans Transplantation
Graft Survival
Islets of Langerhans
Bone Marrow Cells
Transplantation Tolerance
Immune Tolerance
Antilymphocyte Serum
Endocrine Cells
Whole-Body Irradiation
Graft Rejection
Diabetes Complications
Immunosuppressive Agents
Streptozocin
Glucagon
Type 1 Diabetes Mellitus
Cyclophosphamide

All Science Journal Classification (ASJC) codes

  • Surgery
  • Transplantation

Cite this

lee, byungwan ; Lee, J. I. ; Oh, S. H. ; Ahn, Y. R. ; Chae, H. Y. ; Lee, M. S. ; Lee, M. K. ; Kim, K. W. / A more persistent tolerance to islet allografts through bone marrow transplantation in minimal nonmyleoablative conditioning therapy. In: Transplantation Proceedings. 2005 ; Vol. 37, No. 5. pp. 2266-2269.
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abstract = "Introduction. Islet transplantation is a therapeutic approach to prevent diabetes complications. However, the side effects of the required lifelong immunosuppressive regimens to prevent graft rejection restrict the impact of type 1 diabetes. One strategy to overcome these limitations is tolerance induction and graft acceptance through hematopoietic chimerism. In this study we investigated whether tolerance to major histocompability complex (MHC) and minor-disparate islet allografts could be induced by minimal nonmyeloablative conditioning and whether more persistent donor-specific islet allografts were accepted if the grafts were implanted with simultaneous bone marrow cells. Methods. The donor and recipient mice were BALB/c(H-2 b ) and C57BL/6(H-2 d ), respectively. In group 1 streptozotocin-induced diabetic C57BL/6(H-2 d ) mice received only 500 islets of BALB/c(H-2 b ). Group 2 recipients conditioned with antilymphocyte serum, 100 cGy total body irradiation and cyclophosphamide were given islet cells of BALB/c(H-2 b ), but group 3 were simultaneously given 30 × 10 6 BALB/c(H-2 b ) mice BMCs and islet cells similar to group 2. Results. We obtained 5{\%} to 6{\%} allogeneic donor chimerism and 60{\%} graft survival at 80 days after islet transplantation in group 3. We observed lymphocyte infiltration around the islet without destruction of endocrine cells and the presence of strong insulin/glucagon-stained cells in group 3. Conclusion. This minimal nonmyeloablative conditioning therapy induced donor chimerism and immune tolerance between MHC- and minor-disparate (BALB/c→C57BL/6) mice and long-term islet graft survival was obtained through cotransplantation of bone marrow cells.",
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A more persistent tolerance to islet allografts through bone marrow transplantation in minimal nonmyleoablative conditioning therapy. / lee, byungwan; Lee, J. I.; Oh, S. H.; Ahn, Y. R.; Chae, H. Y.; Lee, M. S.; Lee, M. K.; Kim, K. W.

In: Transplantation Proceedings, Vol. 37, No. 5, 01.06.2005, p. 2266-2269.

Research output: Contribution to journalArticle

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T1 - A more persistent tolerance to islet allografts through bone marrow transplantation in minimal nonmyleoablative conditioning therapy

AU - lee, byungwan

AU - Lee, J. I.

AU - Oh, S. H.

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AU - Chae, H. Y.

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N2 - Introduction. Islet transplantation is a therapeutic approach to prevent diabetes complications. However, the side effects of the required lifelong immunosuppressive regimens to prevent graft rejection restrict the impact of type 1 diabetes. One strategy to overcome these limitations is tolerance induction and graft acceptance through hematopoietic chimerism. In this study we investigated whether tolerance to major histocompability complex (MHC) and minor-disparate islet allografts could be induced by minimal nonmyeloablative conditioning and whether more persistent donor-specific islet allografts were accepted if the grafts were implanted with simultaneous bone marrow cells. Methods. The donor and recipient mice were BALB/c(H-2 b ) and C57BL/6(H-2 d ), respectively. In group 1 streptozotocin-induced diabetic C57BL/6(H-2 d ) mice received only 500 islets of BALB/c(H-2 b ). Group 2 recipients conditioned with antilymphocyte serum, 100 cGy total body irradiation and cyclophosphamide were given islet cells of BALB/c(H-2 b ), but group 3 were simultaneously given 30 × 10 6 BALB/c(H-2 b ) mice BMCs and islet cells similar to group 2. Results. We obtained 5% to 6% allogeneic donor chimerism and 60% graft survival at 80 days after islet transplantation in group 3. We observed lymphocyte infiltration around the islet without destruction of endocrine cells and the presence of strong insulin/glucagon-stained cells in group 3. Conclusion. This minimal nonmyeloablative conditioning therapy induced donor chimerism and immune tolerance between MHC- and minor-disparate (BALB/c→C57BL/6) mice and long-term islet graft survival was obtained through cotransplantation of bone marrow cells.

AB - Introduction. Islet transplantation is a therapeutic approach to prevent diabetes complications. However, the side effects of the required lifelong immunosuppressive regimens to prevent graft rejection restrict the impact of type 1 diabetes. One strategy to overcome these limitations is tolerance induction and graft acceptance through hematopoietic chimerism. In this study we investigated whether tolerance to major histocompability complex (MHC) and minor-disparate islet allografts could be induced by minimal nonmyeloablative conditioning and whether more persistent donor-specific islet allografts were accepted if the grafts were implanted with simultaneous bone marrow cells. Methods. The donor and recipient mice were BALB/c(H-2 b ) and C57BL/6(H-2 d ), respectively. In group 1 streptozotocin-induced diabetic C57BL/6(H-2 d ) mice received only 500 islets of BALB/c(H-2 b ). Group 2 recipients conditioned with antilymphocyte serum, 100 cGy total body irradiation and cyclophosphamide were given islet cells of BALB/c(H-2 b ), but group 3 were simultaneously given 30 × 10 6 BALB/c(H-2 b ) mice BMCs and islet cells similar to group 2. Results. We obtained 5% to 6% allogeneic donor chimerism and 60% graft survival at 80 days after islet transplantation in group 3. We observed lymphocyte infiltration around the islet without destruction of endocrine cells and the presence of strong insulin/glucagon-stained cells in group 3. Conclusion. This minimal nonmyeloablative conditioning therapy induced donor chimerism and immune tolerance between MHC- and minor-disparate (BALB/c→C57BL/6) mice and long-term islet graft survival was obtained through cotransplantation of bone marrow cells.

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