- Effects of Islet Transplantation on Endogenous beta-cell Regeneration after Partial Pancreatectomy in Rodents.
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Hye Seung Jung, You Ran Ahn, Seung Hoon Oh, Jung Hwa Jung, Tae Hyun Kim, You Cheol Hwang, Mira Kang, Yongsuk Bae, Young seok Kim, Jae Hoon Chung, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim
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Korean Diabetes J. 2007;31(2):113-122. Published online March 1, 2007
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DOI: https://doi.org/10.4093/jkda.2007.31.2.113
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 Abstract
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- BACKGROUND
Islet transplantation is one of regimens supplying the deficient insulin in diabetes patients, but the effects of islet grafts on the changes of endogenous beta-cells are not clear. In the present study, we examined the changes of endogenous beta-cell mass after islet transplantation in partially pancreatectomized mice. METHODS: Balb/c mice were 70% pancreatectomized, transplanted with syngeneic islets (group IV), and were compared with pancreatectomized mice treated with insulin (group III) or no insulin (group II). Blood glucose levels and body weight were monitored. Remnant pancreas was obtained at 6 or 10 days after pancreatectomy, and immunohistochemical staining was done for the evaluation of beta-cell mass changes. RESULTS: Hyperglycemia and weight loss were induced after pancreatectomy. After islet transplantation or insulin treatment, blood glucose levels recovered to normal, and body weight started to increase. Plasma insulin levels were higher and beta-cell mass was larger in group IV than in group II (P < 0.05). Especially, the difference of beta-cell mass between them was more evident at 7 days as compared to at 3 day after transplantation. When compared to group III, group IV showed larger individual beta-cell area after 7 days and larger beta-cell mass after 3 days of islet transplantation (P < 0.05). CONCLUSION: These observations indicate that islet transplantation plays a role in enhancing remnant beta-cell regeneration after partial pancreatectomy in rodents.
- Effective Glycemic Control Achieved by the Transplantation of VEGF-Transfected Islets in STZ-induced Diabetic Mice.
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Byung Wan Lee, Hee Young Chae, You Ran Ahn, Seung Hoon Oh, Ji Youn Kim, Yun Jae Chung, Sang Young Kim, Kyun Yung Cho, Jae Hoon Chung, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim
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Korean Diabetes J. 2005;29(4):282-294. Published online July 1, 2005
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Abstract
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- BACKGROUND
Hypoxic damage is one of the major causes of early islet graft failure, and VEGF is known to play a crucial role in revascularization. We tried to evaluate whether the VEGF transgene in an islet graft can increase islet revascularization and; therefore, increase the survival rate of transplanted islets in order to achieve effective glycemic control in diabetic mice models using a non-viral cationic lipid reagent for gene delivery into non- dividing islet cells. METHODS: Human VEGF165 cDNA was transfected into Balb/c mice islets using Effectene, and the vascular neogenesis and glucose levels examined in the recipient syngeneic Balb/c mice. A minimal number of VEGF-transfected islets(100 IEQ/animal) were transplanted into STZ-induced diabetic mice. The recipient mice were classified into three groups: islet transplantation(IT) without intervention(IT-alone group, n=8), IT with an islets transduced rhoJDK-control vector(IT-rhoJDK group, n=8), and IT with an islets transduced rhoJDK-VEGF vector(IT-rhoJDK-VEGF group, n=8). RESULTS: The transfection efficiency was highest with 4microgram/microliter cDNA and 25microliter Effectene(1: 6 weight ratio), with satisfactory cell viability under these conditions. The overproductions of VEGF mRNA and proteins from the conditioned cells were confirmed. A minimal number of the VEGF-transfected islets(100 IEQ/animal) were transplanted into STZ-induced diabetic mice. The control of hyperglycemia in the IT-alone(0/8) and IT-rhoJDK groups(0/8) failed. However, complete abrogation of hyperglycemia and viable islets, and an increased vascularization of the VEGF-transfected grafts were identified in the renal capsules of the IT-rhoJDK-VEGF group(8/8). CONCLUSION: These studies support the utility of VEGF-transfected islet delivery using a cationic lipid reagent to achieve euglycemia with minimal islets via neovascularization.
- Induction of Tolerance to Complete Histocompatibility Mismatched Mice Islets through the Co-transplantation of Bone Marrow Cells in a Minimal Nonmyeloablative Condition.
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Ji In Lee, Seung Hoon Oh, You Ran Ahn, Hee Young Chae, Byung Wan Lee, Jae Hoon Chung, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim
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Korean Diabetes J. 2005;29(2):103-111. Published online March 1, 2005
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Abstract
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- 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
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