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Transplantation for the treatment of type 1 diabetes 被引量:3
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作者 R Mark Meloche 《World Journal of Gastroenterology》 SCIE CAS CSCD 2007年第47期6347-6355,共9页
Transplantation of pancreatic tissue, as either the intact whole pancreas or isolated pancreatic islets has become a clinical option to be considered in the treatment of patients with type 1 insulin-dependant diabetes... Transplantation of pancreatic tissue, as either the intact whole pancreas or isolated pancreatic islets has become a clinical option to be considered in the treatment of patients with type 1 insulin-dependant diabetes mellitus. A successful whole pancreas or islet transplant offers the advantages of attaining normal or near normal blood glucose control and normal hemoglobin Alc levels without the risks of severe hypoglycemia associate with intensive insulin therapy. Both forms of transplants are also effective at eliminating the occurrence of significant hypoglycemic events (even with only partial islet function evident). Whereas whole pancreas transplantation has also been shown to be very effective at maintaining a euglycemic state over a sustained period of time, thus providing an opportunity for a recipient to benefit from improvement of their blood glucose control, it is associated with a significant risk of surgical and post-operative complications. Islet transplantation is attractive as a less invasive alternative to whole pancreas transplant and offers the future promise of immunosuppression-free transplantation through pretransplant culture. Islet transplantation however, may not always achieve the sustained level of tight glucose control necessary for reducing the risk of secondary diabetic complications and exposes the patient to the adverse effects of immunosuppression. Although recent advances have led to an increased rate of obtaining insulin-independence following islet transplantation, further developments are needed to improve the longterm viability and function of the graft to maintain improved glucose control over time. 展开更多
关键词 Type 1 diabetes Insulin-dependant diabetes mellitus Pancreas transplantation pancreatic islet transplantation IMMUNOSUPPRESSION Glucose control
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Application of anti-CD103 immunotoxin for saving islet allograft in context of transplantation 被引量:4
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作者 ZHANG Lei Gregg A. Hadley 《Chinese Medical Journal》 SCIE CAS CSCD 2010年第24期3644-3651,共8页
Background Previous studies using knockout mice document a key role for the integrin CD103 in promoting organ allograft rejection and graft-versus-host disease. However, a determination of whether blockade of the CD10... Background Previous studies using knockout mice document a key role for the integrin CD103 in promoting organ allograft rejection and graft-versus-host disease. However, a determination of whether blockade of the CD103 pathway represents a viable therapeutic strategy for intervention in these processes has proven problematic due to the lack of reagents that efficiently deplete CD103+ cells from wild type hosts. To circumvent this problem, in the present study, we invented an anti-CD103 immunotoxin (M290-SAP). We investigated whether M290-SAP has capacity to eliminate CD103-expressing cells in vivo and protect transplanted islets from destroying by host immune cells.Methods Flow cytometry was used to analyze the efficacy of M290-SAP in depleting CD103-expressing cells in vivo.Then using allogenic islet transplantation models as well as NOD mice with recent onset type 1 diabetes, the therapeutic efficacy of CD103-expressing cell depletion was addressed.Results M290-SAP dramatically reduces the frequency and absolute numbers of CD103-expressing leukocytes in peripheral lymphatic tissues of treated mice. Balb/c islets transplanted into streptozotocin-induced diabetic C57BL/6 mice under single M290-SAP treatment showed an indefinite survival time compared with untreated mice, M290-treated mice and IgG-SAP treated mice (mean survival time, >100 days vs. <20 days). C57BL/6 islets transplanted into hyperglycemic NOD mice under single M290-SAP treatment showed a pronounced delay in allograft rejection compared with untreated mice (mean survival time 12-13 days vs. <7 days). Immunological analysis of mice with long-term islet allograft survival revealed an obvious atrophy thymus and severe downregulation of alloimmunity of CD8 subpopulation response to allogenic stimulation.Conclusion Regardless of the underlying mechanisms, these data document that depletion of CD103-expressing cells represents a viable strategy for therapeutic intervention in islet allograft rejection. 展开更多
关键词 IMMUNOTOXIN SAPORIN CD8 T lymphocytes pancreatic islets transplantation THYMUS
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Investigation of long-term preservation of pancreatic islets
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作者 杨华 张秀辉 《Chinese Medical Journal》 SCIE CAS CSCD 1999年第2期8-11,共4页
Objective To develop a method for maintaining viability and function of islets of Langerhans during the long term preservation.Methods We encapsulated Wistar Furth (WF) rat islets in hydrophilic macrobeads (diamet... Objective To develop a method for maintaining viability and function of islets of Langerhans during the long term preservation.Methods We encapsulated Wistar Furth (WF) rat islets in hydrophilic macrobeads (diameter 6-8 mm) made with agarose and collagen, then preserved them at 37℃ in a humidified atmosphere of air and 5% CO 2 for different time, and compared unencapsulated islets with encapsulated islets for their insulin secretion capability in vitro. At the same time, we have investigated their viability and insulin secreting function in vivo.Results Initially, there was no statistically significant difference in the insulin secretion values between the encapsulated and unencapsulated WF rat islets. While the unencapsulated islet insulin secretion decreased significantly within 2 weeks, the preserved and encapsulated islets maintained their viability and ability of insulin secretion for 40 weeks. In the in vivo study, the diabetic state was reversed in 92.8% of recipients transplanted with preserved macroencapsulated islets. The mice maintained normoglycemia for 157.6±49.3 days, at which point these macrobeads were retrieved. Glucose tolerance curves in the recipient mice were similar to those of normal mice. Conclusions These results indicate that it is a good method for long term preservation of islets by encapsulating islets in agarose and collagen, and then culturing them at 37℃ in a humidified atmosphere of air and 5% CO 2 before transplantation. 展开更多
关键词 pancreatic islets · insulin · preservation · transplantation
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Hemo oxygenase-1 induction in vitro and in vivo can yield pancreas islet xenograft survival and improve islet function 被引量:2
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作者 CHEN Xi SU Chang +5 位作者 ZHANG Zheng-yun ZHANG Ming-jun GU Wei-qiong LI Xiao-ying LI Hong-wei ZHOU Guang-wen 《Chinese Medical Journal》 SCIE CAS CSCD 2011年第20期3378-3385,共8页
Background The induced expression of heme oxygenase-1 (HO-1) in donor islets improves allograft survival. Cobalt protoporphyrin (CoPP) could significantly enhance the expression of HO-1 mRNA and protein in rat isl... Background The induced expression of heme oxygenase-1 (HO-1) in donor islets improves allograft survival. Cobalt protoporphyrin (CoPP) could significantly enhance the expression of HO-1 mRNA and protein in rat islet safely. Our work was to study how to protect pancreatic islet xenograft by CoPP-induction. Methods Islet xenografts treated with CoPP-induction and CoPP+ Zinc protoporphyrin (ZnPP) in vitro and in vivo were randomly transplanted into murine subrenal capsule; then the graft survival time was compared by blood glucose level and pathological examination and meanwhile the interferon ~ (IFN-y), tumor necrosis factor a (TNF-a), interleukin 10 (IL-10) and IL-113 level in serum and their mRNA and HO-1 mRNA and protein expression were examined. Results Islets with CoPP-induction under low- and high-glucose stimulation exhibited much higher insulin secretion compared with other three groups. CoPP-induction could increase higher expression of HO-1 (mRNA: 3.33- and 76.09- fold in vitro and in vivo; protein: 2.85- and 58.72-fold). The normoglycemia time in induction groups ((14.63±1.19) and (16.88±1.64) days) was significantly longer. The pathological examination showed less lymphocyte infiltration in induction groups. The IL-10 level and its mRNA in induction groups were significantly higher. Conclusions The HO-1 induced by CoPP would significantly improve function, prolong normoglycemia time and reduce lymphocyte infiltration. Meanwhile CoPP-induction in vivo had more beneficial effects than in vitro. Its mechanism could be related to immune-modulation of IL-10. 展开更多
关键词 pancreatic islet transplantation cobalt protoporphyrin XENOGRAFT heme oxygenase interleukin 10
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