Prolonged Survival of Subcutaneous Allogeneic Islet Graft by Donor Chimerism without Immunosuppressive Treatment

The aim of this study was to investigate whether tolerance-induced protection of islets in the renal subcapsular space can also prevent subcutaneous allogeneic islets from being rejected. We used bone marrow stem cells from C57BL/6 (H2b) mice to construct donor chimerism in conditioned diabetic BALB...

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Main Authors: Brend Ray-Sea Hsu, Shin-Huei Fu, Aline Yen Ling Wang
Format: Article
Language:English
Published: Wiley 2017-01-01
Series:International Journal of Endocrinology
Online Access:http://dx.doi.org/10.1155/2017/7057852
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author Brend Ray-Sea Hsu
Shin-Huei Fu
Aline Yen Ling Wang
author_facet Brend Ray-Sea Hsu
Shin-Huei Fu
Aline Yen Ling Wang
author_sort Brend Ray-Sea Hsu
collection DOAJ
description The aim of this study was to investigate whether tolerance-induced protection of islets in the renal subcapsular space can also prevent subcutaneous allogeneic islets from being rejected. We used bone marrow stem cells from C57BL/6 (H2b) mice to construct donor chimerism in conditioned diabetic BALB/c (H2d) mice and investigated the effect of donor chimerism on engraftment and survival of subcutaneously transplanted allogeneic islets in streptozotocin-induced diabetic mice. We also studied the anti-inflammatory effect of mesenchymal stem cell on islet engraftment. Full but not low-grade or no donor chimerism was associated with successful engraftment of allogeneic islets and restoration of normoglycemia in the treated diabetic mice. The temporary hyperglycemia was 11 ± 1 versus 19 ± 5 days (p<0.05) for the mice with full donor chimerism with transplanted islets in the renal subcapsular space versus the subcutaneous space, respectively. Cotransplantation of mesenchymal stem cell did not enhance alloislet engraftment. Full multilineage donor chimerism was associated with a higher transient expansion of CD11b+ and Gr-1+ myeloid progenitor cells and effector memory CD4 and CD8 T cells. In conclusion, full donor chimerism protected both renal subcapsular and subcutaneous allogeneic islets in this rodent transplantation model.
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publishDate 2017-01-01
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spelling doaj-art-1b4ce00a58e64092a125294e8af0f0262025-08-20T03:54:24ZengWileyInternational Journal of Endocrinology1687-83371687-83452017-01-01201710.1155/2017/70578527057852Prolonged Survival of Subcutaneous Allogeneic Islet Graft by Donor Chimerism without Immunosuppressive TreatmentBrend Ray-Sea Hsu0Shin-Huei Fu1Aline Yen Ling Wang2Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Medical Center, Taoyuan, TaiwanDepartment and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei, TaiwanCenter for Vascularized Composite Allotransplantation, Chang Gung Memorial Hospital, Taoyuan, TaiwanThe aim of this study was to investigate whether tolerance-induced protection of islets in the renal subcapsular space can also prevent subcutaneous allogeneic islets from being rejected. We used bone marrow stem cells from C57BL/6 (H2b) mice to construct donor chimerism in conditioned diabetic BALB/c (H2d) mice and investigated the effect of donor chimerism on engraftment and survival of subcutaneously transplanted allogeneic islets in streptozotocin-induced diabetic mice. We also studied the anti-inflammatory effect of mesenchymal stem cell on islet engraftment. Full but not low-grade or no donor chimerism was associated with successful engraftment of allogeneic islets and restoration of normoglycemia in the treated diabetic mice. The temporary hyperglycemia was 11 ± 1 versus 19 ± 5 days (p<0.05) for the mice with full donor chimerism with transplanted islets in the renal subcapsular space versus the subcutaneous space, respectively. Cotransplantation of mesenchymal stem cell did not enhance alloislet engraftment. Full multilineage donor chimerism was associated with a higher transient expansion of CD11b+ and Gr-1+ myeloid progenitor cells and effector memory CD4 and CD8 T cells. In conclusion, full donor chimerism protected both renal subcapsular and subcutaneous allogeneic islets in this rodent transplantation model.http://dx.doi.org/10.1155/2017/7057852
spellingShingle Brend Ray-Sea Hsu
Shin-Huei Fu
Aline Yen Ling Wang
Prolonged Survival of Subcutaneous Allogeneic Islet Graft by Donor Chimerism without Immunosuppressive Treatment
International Journal of Endocrinology
title Prolonged Survival of Subcutaneous Allogeneic Islet Graft by Donor Chimerism without Immunosuppressive Treatment
title_full Prolonged Survival of Subcutaneous Allogeneic Islet Graft by Donor Chimerism without Immunosuppressive Treatment
title_fullStr Prolonged Survival of Subcutaneous Allogeneic Islet Graft by Donor Chimerism without Immunosuppressive Treatment
title_full_unstemmed Prolonged Survival of Subcutaneous Allogeneic Islet Graft by Donor Chimerism without Immunosuppressive Treatment
title_short Prolonged Survival of Subcutaneous Allogeneic Islet Graft by Donor Chimerism without Immunosuppressive Treatment
title_sort prolonged survival of subcutaneous allogeneic islet graft by donor chimerism without immunosuppressive treatment
url http://dx.doi.org/10.1155/2017/7057852
work_keys_str_mv AT brendrayseahsu prolongedsurvivalofsubcutaneousallogeneicisletgraftbydonorchimerismwithoutimmunosuppressivetreatment
AT shinhueifu prolongedsurvivalofsubcutaneousallogeneicisletgraftbydonorchimerismwithoutimmunosuppressivetreatment
AT alineyenlingwang prolongedsurvivalofsubcutaneousallogeneicisletgraftbydonorchimerismwithoutimmunosuppressivetreatment