Browsing by Author "Juang, J. -H."

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Coculture of Hepatocytes with Islets
(2011-11-01)
Kuo, C. -H.
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Juang, J. -H.
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Peng, H. -L.
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生物科技學系
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Department of Biological Science and Technology
Bioartificial liver support (BAL) systems are potential new therapeutic approaches for use as liver support to prevent nutrient deficiencies, hypoxia, or ischemia before the acquisition of donated organs. To investigate whether islets are beneficial for hepatocyte function and survival, we cocultured BALB/c mouse islets with C57BL/6J hepatocytes to assess hepatocyte viability, function, and apoptosis. We observe cell viability to decrease progressively by 50% from day 0 to day 3 among isolated hepatocytes (group A) and hepatocytes cocultured with islets (group B). However, group A was prone to necrosis and reduced albumin secretion during culture. In contrast, at day 7 group B maintained albumin secretion (0.3351 +/- 0.0581 vs 0.1451 +/- 0.0329 mu g/h/mL; P <.05). Early apoptosis was observed at day 3 among group A but at day 7 in group B. In addition, quantitative analysis of the apoptotic cells revealed group B to show a delayed phenotype of both early and late apoptosis compared with group A. Our results indicated that islets could retain hepatocyte function and delay apoptosis, suggesting that the coculture system is potentially applicable to develop a high-performance BAL.
Effects of Cyclooxygenase-2 Inhibitor and Adenosine Triphosphate-Sensitive Potassium Channel Opener in Syngeneic Mouse Islet Transplantation
(2010-12-01)
Juang, J. -H.
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Kuo, C. -H.
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生物科技學系
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Department of Biological Science and Technology
In the initial days after transplantation, islet grafts may be attacked by cytokines via cyclooxygenase-2 (COX-2), producing primary nonfunction. In addition, chronic overstimulation of beta-cells may impair insulin secretion. To enhance the function of transplanted islets, the present study investigated the effects of rofecoxib, a COX-2 inhibitor, and NN414 (6-chloro-3[1-methylcyclopropyl]amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide), an adenosine triphosphate-sensitive potassium channel opener, on islet transplantation. Male inbred C57BL/6 mice were used as donors and recipients. One hundred fifty islets were isolated via collagenase digestion and density gradient, and syngeneically transplanted under the kidney capsule in mice with streptozotocin-induced diabetes. Recipients were treated with or without rofecoxib, 10 mg/kg/d orally, or with or without NN414, 3 mg/kg/d orally, for 4 weeks. After transplantation, recipient body weight, blood glucose concentration, and intraperitoneal glucose tolerance were measured. The grafted kidney was extracted for determination of insulin content at 4 weeks. In the rofecoxib-treated and NN414-treated groups and both control groups, body weight remained stable, and the blood glucose concentration decreased progressively. However, at 4 weeks after transplantation in the groups treated or not treated with rofecoxib or NN414, no significant difference was observed in recipient body weight, blood glucose concentration, and glucose tolerance or in insulin content of the graft. These data indicate that posttransplantation treatment with rofecoxib or NN414 has no beneficial effect on transplantation outcome in diabetic mouse recipients engrafted with a marginal islet mass.
Effects of dipeptidyl peptidase 4 inhibition with MK-0431 on syngeneic mouse islet transplantation
(2011-09-01)
Juang, J. -H.
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Kuo, C. -H.
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Liu, Y. -H.
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Chen, C. -T.
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生物科技學系
Effects of Insulin-Like Growth Factor-1 and Donor Age on Transplantation of Porcine Neonatal Pancreatic Cell Clusters
(2009-06-01)
Juang, J. -H.
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Kuo, C. -H.
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Yao, N. -K.
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生物科技學系
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Department of Biological Science and Technology
Porcine neonatal pancreatic cell clusters (NPCCs) isolated from 1- to 3-day-old pigs cured diabetic nude mice more than 14 weeks after transplantation. To shorten the latent period between transplantation and reversal of hyperglycemia, we investigated the effects of insulin-like growth factor-1 (IGF-1) and NPCCs isolated from 1-month-old pigs after transplantation. Pig pancreata were cut into fragments, collagenase digested, and then cultured. Three hundred and 2000 NPCCs were transplanted under the kidney capsule of nondiabetic and diabetic nude mice, respectively. After transplantation, the graft-bearing kidneys were removed to measure insulin content. NPCCs isolated from 1- to 3-day-old pigs were cultured with or without IGF-1 for 6 days. The stimulation index was not significantly different between the 2 groups at 1, 2, or 4 weeks. Moreover, at 4 weeks after transplantation of 300 NPCCs to nondiabetic nude mice yielded comparable graft insulin content as the recipients of NPCCs precultured with or without IGF-1. Two thousand cultured NPCCs isolated from 1-to 3-day-old pigs or 1-month-old pigs were transplanted into diabetic nude mice. The blood glucose levels of diabetic recipients in both groups decreased at the same rate after transplantation, achieving normoglycemia at 8 weeks. The graft insulin content at 12 weeks was not different between the 2 groups. Our data indicated that isolated NPCCs cultured with IGF-1 showed no beneficial effects on insulin secretion and transplantation; NPCCs isolated from 1-to 3-day-old and 1-month-old pigs displayed similar effects on transplantation.
Magnetic Resonance Imaging Study of Mouse Islet Allotransplantation
(2010-12-01)
Juang, J. -H.
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Shen, C. -R.
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Wang, J. -J.
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Kuo, C. -H.
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Lin, M. -Y.
Although only 10% of islet transplant recipients maintain insulin independence, 80% of them are C-peptide positive at 5 years. To better understand the fate of transplanted islets, a magnetic resonance imaging (MRI) technique has been used to detect superparamagnetic iron oxide (SPIO) labeled transplanted islets. Recently, we successfully used a novel MRI contrast agent, chitosan-coated SPIO (CSPIO) nanoparticles, to monitor mouse islet isografts for 18 weeks after transplantation. In the present study, we tested whether CSPIO could be applied to monitor islet allografts, which are supposedly rejected without immune interventions. Male C57BL/6 and Balb/c mice were used as donors and recipients of islet transplantation, respectively. After overnight incubation with or without CSPIO (10 mu g/mL), 300 C57BL/6 islets were transplanted under the left kidney capsule of each Balb/c mouse. Starting from day 10 after transplantation, 3.0-Tesla MRI of the recipients was performed weekly. Four mice were followed for >= 38 days. At 38 and 45 days, 1 islet graft was removed for insulin and Prussian blue staining, respectively. From days 10 to 45 after transplantation, CSPIO-labeled islet grafts were visualized on MRI scans as sustained distinct hypointense spots homogeneously located at the upper pole of left kidney, the site of transplantation. At days 38 and 45, the histology of CSPIO-labeled islet grafts revealed insulin and iron staining colocalized in the same areas. Our results in a mouse allotransplantation model indicated that CSPIO-labeled islets survived as long as 45 days with positive MRI.
Modest Effects of Fas-Ligand and Heme Oxygenase-1 Double Transgenic Mouse Islets on Transplantation Outcomes
(2011-11-01)
Juang, J. -H.
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Tu, C. -F.
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Kuo, C. -H.
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生物科技學系
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Department of Biological Science and Technology
Interactions of Fas with its ligand (FasL) play an important role in the maintenance of immunologic homeostasis and peripheral tolerance. Heme oxygenase-1 (HO-1) is a protein capable of cytoprotection via radical scavenging and apoptosis prevention. The aim of this study was to test whether overexpression of FasL and HO-1 in murine islets resulted in cell protection and improved functional performance after transplantation. We first generated FasL and HO-1 double transgenic mice to investigate the protective effect of transgenic islets on transplantation. Islets were isolated from FasL and HO-1 double transgenic and nontransgenic Balb/c mice, for transplantation of 300 islets under the left kidney capsule of each streptozotocin-diabetic Balb/c mouse. During 6 weeks after transplantation, the blood glucose gradually decreased in recipients of double transgenic and nontransgenic islets. However, the decrease in blood glucose was more pronounced in the former (450 +/- 16 mg/dL at day 0 to 302 +/- 55 mg/dL at day 42; P =.01) than the latter (468 +/- 17 mg/dL at day 0 to 379 +/- 71 mg/dL at day 42; P =.24). The areas under the curve of intraperitoneal glucose tolerance tests at 2, 4, and 6 weeks were not significantly different between recipients of double transgenic and nontransgenic islets. The body weight increased in recipients of double transgenic islets (21.1 +/- 1.4 g at day 0 to 26.2 +/- 0.8 g at day 42; P =.0002) and nontransgenic islets (21.0 +/- 1.4 g at day 0 to 25.1 +/- 0.4 g at day 42; P =.0448). Our data suggested modest beneficial effects of transgenic islets with FasL and HO-1 overexpression for transplantation.
Tracking mouse islet isografts and allografts using a novel magnetic resonance contrast agent, chitosan-coated superparamagnetic iron oxide nanoparticles
(2010-09-01)
Juang, J. -H.
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Shen, C. -R.
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Wang, J. -J.
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Kuo, C. -H.
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Tsai, Z. -T.