Permanent protection of PLG scaffold transplanted allogeneic islet grafts in diabetic mice treated with ECDI-fixed donor splenocyte infusions

Allogeneic islet cell transplantation is a promising treatment for human type 1 diabetes. Currently, human islets are transplanted via intra-portal infusions. While successful, it leads to significant early islet attrition from instant blood-mediated inflammatory reaction. An extra-hepatic site was established by transplanting islet-loaded microporous poly(lactide-co-glycolide) (PLG) scaffolds into the epididymal fat pad in syngeneic islet transplant models. This study examined this technology in allogeneic islet transplantation and determined whether transplant tolerance could be effectively induced to protect PLG scaffold transplanted allogeneic islets. The efficacy of an established tolerance induction strategy using donor splenocytes treated with ethylcarbodiimide(ECDI) was tested. ECDI-fixed donor splenocytes were infused 7 days before and 1 day after islet transplantation. Immediate normoglycemia was restored, and treated mice maintained indefinite normoglycemia whereas untreated mice rejected islet grafts within 20 days of transplantation. Interestingly, efficacy of tolerance induction was superior in PLG scaffold compared with intra-portal transplanted islets. Protection of PLG scaffold islet allografts was associated with several mechanisms of immune regulation. In summary, PLG scaffolds can serve as an alternative delivery system for islet transplantation that does not impair tolerance induction. This approach of combining tolerance induction with scaffold islet transplantation has potential therapeutic implications for human islet transplantation.     

That which does not kill us makes us stronger – Does Nietzsche’s quote apply to islets? A re-evaluation of the passenger leukocyte theory,free radicals,and glucose toxicity in islet cell transplantation

In clinical islet transplantation, isolated islets are embolized into the liver via the portal vein (PV); however, up to 70% of the islets are lost in the first few days after transplantation (i.e., too quickly to be mediated by the adaptive immune system). Part of early loss is due to instant blood-mediated inflammatory reaction, an immune/thrombotic process caused by islets interacting with complement. We have shown that glucose toxicity (GT) also plays a critical role based upon the observation that islets embolized into the PVs of diabetic athymic mice are rapidly lost but, if recipients are not diabetic, the islet grafts persist. Using donor islets resistant to the β-cell toxin streptozotocin, we have shown that intraportal islets engrafted in non-diabetic athymic mice for as little as 3 days will maintain normoglycemia when streptozotocin is administered destroying the recipient’s native pancreas β-cells. What is the mechanism of GT in β-cells? Chronic exposure to hyperglycemia over-exerts β-cells and their electron transport chains leak superoxide radicals during aerobic metabolism. Here we reinterpret old data and present some compelling new data supporting a new model of early intraportal islet graft loss. We hypothesize that diabetes stimulates overproduction of superoxide in both the β-cells of the islet grafts and the endothelial cells lining the intraportal microvasculature adjacent to where the embolized islets become lodged. This double dose of oxidant damage stresses both the islets, which are highly susceptible to free radicals because of inherent low levels of scavenging enzymes, and the adjacent hepatic endothelial cells. This, superimposed upon localized endothelial damage caused by embolization, precipitates inflammation and coagulation which further damages islet grafts. Based upon this model, we predict that pre-exposing islets to sub-lethal hyperoxia should up-regulate islet free radical scavenging enzyme levels and promote initial engraftment; reinterpretation of 30 years old “passenger leukocyte” data and preliminary new data support this. Other data suggests that pre-exposure of recipients to hyperoxia could up-regulate antioxidant enzymes in the hepatic endothelium. The combination of both effects could markedly enhance early intraportal islet graft survival and engraftment. Finally, if our model is correct, current in vitro and in vivo tests used to test batches of harvested islets for viability and function prior to transplantation are poorly conceived (n.b., it is already well-known that results using these tests often do not predict clinical islet transplantation success) and a different testing paradigm is suggested.     

Development of an ectopic site for islet transplantation, using biodegradable scaffolds

Clinical islet transplantation in liver has achieved normoglycemia. However, this site may not be ideal for islet survival. To create a more optimal site for islet transplantation, we have developed a construct with biodegradable scaffolds. Islets were seeded in scaffolds and transplanted into the epididymal fat pad of diabetic BALB/c mice. Controls included islets transplanted underneath the kidney capsule or into the fat pad without scaffolds. All animals with islets in scaffolds or the kidney became normoglycemic and maintained this metabolic state. When islets were transplanted without scaffolds the time to achieve normoglycemia was significantly increased and less than 45% of mice survived. An oral glucose tolerance test was performed on the scaffold and kidney groups with similar blood glucose levels and area under the curve values between the groups. Grafts were removed at more than 100 days posttransplantation and all animals became hyperglycemic. There was no significant difference in insulin content between the grafts and all grafts were well vascularized with insulin-positive beta cells. Therefore, islets in scaffolds function and restore diabetic animals to normoglycemic levels, similar to islets transplanted underneath the kidney capsule, suggesting scaffolds can be used to create a site for islet transplantation.     

Small islets are essential for successful intraportal transplantation in a diabetes mouse model

Optimization of islet transplantation protocols is necessary for improved success of treatment for type 1 diabetes. Here, we investigated whether the size of islets transplanted into the portal vein (PV) of the liver can affect engraftment in the early post-transplantation in an experimental mouse model. Small (average diameter < 250 μm, group A) or large (average diameter > 250 μm, group B) islets (400 islet equivalents/recipient) purified from normal BALB/c mice were transplanted into syngenic recipients with diabetes induced by STZ. The percentage of mice returning to a non-diabetic status was higher in group A (100%) than that of group B (62.5%). Focal areas of liver necrosis associated with the islets emboli were observed in both groups, but the pathology in group B was significantly worse. Multiple proinflammatory cytokines were significantly higher in group B than that of A at 3 h post-transplantation. Our study determined that the size of islets plays a critical role in the success of intraportal islet transplantation (IPIT) and should be taken into account in future IPIT protocols for the treatment of diabetes.     

Islet‐expressed TLR2 and TLR4 sense injury and mediate early graft failure after transplantation

Although islet transplantation is an effective treatment for Type 1 diabetes, primary engraftment failure contributes to suboptimal outcomes. We tested the hypothesis that islet isolation and transplantation activate innate immunity through TLR expressed on islets. Murine islets constitutively express TLR2 and TLR4, and TLR activation with peptidoglycan or LPS upregulates islet production of cytokines and chemokines. Following transplantation into streptozotocin‐induced diabetic, syngeneic mice, islets exposed to LPS or peptidoglycan had primary graft failure with intra‐ and peri‐islet mononuclear cell inflammation. The use of knockout mice showed that recipient CD8⁺ T cells caused engraftment failure and did so in the absence of islet‐derived DC. To mimic physiological islet injury, islets were transplanted with exocrine debris. Transplantation of TLR2/4^?/? islets reduced proinflammatory cytokine production and improved islet survival. Stressed islets released the alarmin high‐mobility group box protein 1 (HMGB1) and recombinant HMGB1 (rHMGB1) induced NFkB activation. NFkB activation was prevented in the absence of both TLR2 and TLR4. rHMGB1 pretreatment also prevented primary engraftment through a TLR2/4‐dependent pathway. Our results show that islet graft failure can be initiated by TLR2 and TLR4 signaling and suggest that HMGB1 is one likely early mediator. Subsequent downstream signaling results in intra‐islet inflammation followed by T‐cell‐mediated graft destruction.     

胰岛移植高分子生物材料支架研究进展

肝脏可能不是胰岛移植最理想的环境,肝内胰岛移植相关的问题阻碍其广泛应用。体内许多部位都曾被尝试用来作为胰岛移植的替代位点,但到目前为止还没有找到一个最适宜胰岛移植的部位。开发生物工程材料支架用于肝外胰岛移植可能是一种理想的选择。概述近3年胰岛移植高分子生物材料支架的研究现状,包括天然高分子材料支架、人工高分子材料支架、人工-天然复合材料支架、全器官脱细胞支架和3D生物打印支架,最后对其前景进行展望。     

Ultrastructural evidence for blood microvessels devoid of an endothelial cell lining in transplanted pancreatic islets.

The aim of the present study was to investigate, at the ultrastructural level, the process of revascularization of freshly isolated islets or cultured islets after transplantation under the kidney capsule of syngeneic mice. Native islets in adult pancreases from mice, pigs, and humans contained only capillaries with fenestrated endothelium. However, the endothelial cell lining was disrupted in both freshly isolated and cultured mouse islets. Shortly after transplantation (6 weeks) approximately 80% of graft microvessels contained no endothelial cell lining. Similar data on microvessel morphology were found when fetal porcine islet-like cell clusters were implanted into athymic nude mice. Re-endothelialization was a slow process, with 25% of the microvessels still lacking endothelium 6 months after transplantation of cultured mouse islets or islet-like cell cluster. However, when freshly isolated mouse islets are used only 25% of microvessels within the islet graft lacked endothelium 6 weeks after implantation. We suggest that capillaries damaged during islet isolation may provide a preformed channel, serving as a scaffold for newly formed islet graft blood vessels. The presence of non-endothelialized microvessels, with an associated lack of barrier function, might make transplanted islets more prone to thrombosis or an attack by the immune system. This provides a tentative explanation for the increased vulnerability of islet grafts when compared with whole pancreas transplants.     

Islet Mass Plays a Critical Role in Initiation, but not Progression, of the Diabetogenic Process in NOD Mice

Pancreatectomy (90%) at a preinsulitis age (7 weeks) protects NOD mice from diabetes while pancreatectomy at a mid-insulitis age (13 weeks) has no such protective effect. The present study examined the effects of islet transplantation in pancreatectomized diabetes-free NOD mice. Transplantation of syngeneic NOD islets as well as allogeneic C3H/He and C57BL/6 islets 3 weeks after pancreatectomy-induced spontaneous diabetes whereas transplantation of xenogeneic Sprague-Dawley rat islets or allogeneic C3H/He skin failed to induce diabetes, demonstrating that the diabetogenic antigen(s) of NOD islets is also expressed by islets of diabetes-resistant mouse strains but not by xenogeneic rat islets. Removal of NOD islet grafts by nephrectomy 7-14 days after transplantation had no effect on the subsequent chronic development of diabetes, while graft removal 3 days after transplantation completely abolished the diabetogenic effect of islet transplantation. Thus, activation of the diabetogenic response by islet isografting takes less than 7 days and the continuous presence of a large islet mass is not required for progression to diabetes. While islet transplantation at 10 and 15 weeks of age caused diabetes, delayed islet transplantation at 23 and 35 weeks of age failed to induce diabetes in pancreatectomized diabetes-free NOD mice, suggesting that initiation of the diabetogenic autoimmune process must take place within a certain window of time. The pancreatectomy/islet transplantation model is excellent for studying the immunological events surrounding activation and progression of the diabetogenic autoimmune process and for identifying the diabetogenic islet antigen(s).     

MRI of transplanted surface-labeled pancreatic islets with heparinized superparamagnetic iron oxide nanoparticles

Transplantation of insulin-secreting pancreatic islets can provide real-time regulation of blood glucose in patients with type 1 diabetes mellitus. Currently, noninvasive and repetitive monitoring of islet engraftment and function is an emerging and promising modality for successful islet transplantation. Here we report a new technique for highly sensitive in?vivo magnetic resonance (MR) imaging of transplanted pancreatic islets. To this end, heparinized superparamagnetic iron oxide (heparin-SPIO) nanoparticle was newly synthesized for chemical conjugation onto islet surface. Compared to typical cellular labeling of Feridex(?) via random endocytosis, chemical conjugation of heparin-SPIO was stable and improved the hypointensity of transplanted islets due to surface modification of every islet. These heparin-SPIO-conjugated islets showed normal viability and insulin secretion, and were quantified by spin echo T(2)-weighted MR imaging with linear correlation depending on transplanted islet mass in?vitro and in?vivo for 30 days. Also, from the immunohistochemistry, we confirmed the existence of heparin-SPIO and insulin biosynthesis in transplanted islets. However, Feridex-uptake islets showed late glucose responsiveness according to changing glucose concentration although they could normally control the blood glucose levels in diabetic mouse. Thus, we anticipate that this surface labeling with heparin-SPIO can be directly applicable for MR imaging of transplanted islets.     

Isokinetic gradient centrifugation prolongs survival of pig islets xenografted into mice

Highly purified porcine islets were prepared by isokinetic gradients performed subsequently to isopycnic gradients. This additional purification step separates ductal, vascular, and lymphoid tissue effectively from endocrine tissue. Although ductal, vascular, and lymphoid tissue comprises only a minor contamination of the islet suspensions, a significant prolongation of the survival of porcine islets xenografted into streptozotocin diabetic C57BL/6 mice can be achieved by the elimination of the non-endocrine tissue. Rejection after islet transplantation is delayed from 2.2±0.4 days (n=27) to 13.1±2.1 days (n=36), respectiveley, when conventionally purified and highly purified islets are compared. Irrespective of the purification state, pretreatment of islets by low temperature culture had no effect on xenograft survival.     

Application of an endothelialized modular construct for islet transplantation in syngeneic and allogeneic immunosuppressed rat models

Modular tissue engineering is a novel approach to assemble tissues with an inherent vascularization. In this article, we evaluated whether endothelialized module-driven vascularization enhances islet engraftment in diabetic rats. Two thousand islets were transplanted in the omental pouch of syngeneic and allogeneic immunosuppressed diabetic recipients as free islets, islets in collagen modules, or islets in endothelialized modules. Transplantation of islets in endothelialized modules significantly increased the vessel density compared with controls. Donor green fluorescent protein-positive endothelial cells (ECs) formed vessels in proximity to transplanted islets; donor vessels connected to host vasculature as the vessels included erythrocytes in their lumens and were supported by host smooth muscle cells by 21 days. Transplantation of 2000 islets reversed diabetes in two of five of syngeneic recipients until 60 days, although there was no apparent benefit to islet function of adding ECs relative to collagen modules without EC. However, there was a trend toward increased viability when islets were implanted in endothelialized modules compared with collagen modules at 21 days. Meanwhile, 2000 islets in allogeneic immunosuppressed recipients lowered blood glucose levels short term, but there was graft failure within 1 week. This study explored the simultaneous transplantation of primary ECs with islets in diabetic recipients. The endothelialized modular approach increased vessel density around transplanted islets. Further modulation (i.e., acceleration) of vessel maturation, is presumed necessary to improve islet engraftment.     

Plasma-fibroblast gel as scaffold for islet transplantation

The transplant of pancreatic islets into the liver can restore normal blood glucose levels in patients with type I diabetes. However, long-term results have indicated that the site and method of transplantation still need to be optimized to improve islet engraftment. This study was designed to assess the efficiency of the use of clotted blood plasma containing fibroblasts ("plasma-fibroblast gel") as a scaffold for subcutaneous islet transplantation in diabetic athymic mice. Islets embedded in the plasma-fibroblast gel were able to resolve hyperglycemia in transplanted mice, restoring normoglycemia over a 60-day period and allowing gradual body weight recovery. Glucose clearances were significantly improved when compared to those recorded in diabetic animals and similar to those observed in the control group (free islets transplanted beneath the kidney capsule). Histological evaluation revealed functional islets within a subcutaneous tissue rich in collagen fibers that was well vascularized, with blood vessels observed around and inside the islets. These findings suggest that this approach could be used as an alternative option for the treatment of type I diabetes in human clinical practice.     

Would blockage of cytokines improve the outcome of pancreatic islet transplantation?

It has been estimated that up to 60% of pancreatic islet tissue undergoes apoptosis within the first several days post-transplantation. This strongly suggests the involvement of an inflammatory event other than alloantigen-specific immune reaction following islet transplantation which contributes to partial destruction of grafts. Inflammatory cytokines including IL-1beta, TNF-alpha and IFN-gamma are implicated in the pancreatic islet beta-cell death and functional loss during autoimmune diabetes and also seem to be involved in early loss of islet mass in islet transplantation. Inflammatory cytokines and free oxygen radicals released in situ could cause apoptosis and the functional impairment of islets after islet transplantation and graft failure. It can be hypothesized that preventing destruction of transplanted islets using cytokine blockade could be helpful in improving islet transplantation outcome. Several approaches have been made based on this hypothesis to examine the effect of inflammatory blockade on the islets survival and functional islet mass. Further investigations are required to identify most efficient way for block of cytokine-induced damage in pancreatic islets transplantation.     

Mouse Pancreatic Islets Are Resistant to Indoleamine 2,3 Dioxygenase-Induced General Control Nonderepressible-2 Kinase Stress Pathway and Maintain Normal Viability and Function

Islet transplantation is a promising treatment for diabetes. However, it faces several challenges including requirement of systemic immunosuppression. Indoleamine 2,3-dioxygenase (IDO), a tryptophan degrading enzyme, is a potent immunomodulatory factor. Local expression of IDO in bystander fibroblasts suppresses islet allogeneic immune response in vitro. The aim of the present study was to investigate the impact of IDO on viability and function of mouse islets embedded within IDO-expressing fibroblast-populated collagen scaffold. Mouse islets were embedded within collagen matrix populated with IDO adenovector-transduced or control fibroblasts. Proliferation, insulin content, glucose responsiveness, and activation of general control nonderepressible-2 kinase stress-responsive pathway were then measured in IDO-exposed islets. In vivo viabilities of composite islet grafts were also tested in a syngeneic diabetic animal model. No reduction in islet cells proliferation was detected in both IDO-expressing and control composites compared to the baseline rates. Islet functional studies showed normal insulin content and secretion in both preparations. In contrast to lymphocytes, general control nonderepressible-2 kinase pathway was not activated in islets cocultured with IDO-expressing fibroblasts. When transplanted to diabetic mice, syngeneic IDO-expressing composite islet grafts were functional up to 100 days tested. These findings collectively confirm normal viability and functionality of islets cocultured with IDO-expressing cells and indicate the feasibility of development of a functional nonrejectable islet graft.     

胎鼠胰腺干细胞与胰岛联合移植保护胰岛

背景：胰腺干细胞可在体外维持胰岛的结构,减少胰岛细胞坏死及凋亡,延长胰岛的体外存活时间,保护胰岛的活性。 目的：探索胎鼠胰腺干细胞与胰岛共移植体内保护移植胰岛,提高胰岛移植疗效的可行性。 方法：将成年大鼠35只随机等分为联合移植组、单独胰岛移植组、单纯胰腺干细胞移植组、模型组及对照组,前4组均腹腔注射链脲佐菌素-柠檬酸盐缓冲液建立糖尿病模型。联合移植组、单独胰岛移植组、单纯胰腺干细胞大鼠分别在左侧肾包膜下移植分离纯化孕16 d SD大鼠胎鼠胰腺干细胞和/或成年SD大鼠胰岛。 结果与结论：联合移植组大鼠移植后5 d内血糖可降至正常,血浆胰岛素达到正常水平,胰岛存活时间(18.2±2.4) d;单独移植组大鼠血糖可于移植后1周内降至正常,胰岛存活时间(14.4±2.1) d;两组胰岛存活时间比较差异有显著性意义(P < 0.05)。而其他组糖尿病大鼠血糖均未能降至正常范围。说明胎鼠胰腺干细胞与胰岛共移植可延长胰岛体内存活时间,保护胰岛功能,提高移植疗效。中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程全文链接：     

Surface modification of pancreatic islets using heparin-DOPA conjugate and anti-CD154 mAb for the prolonged survival of intrahepatic transplanted islets in a xenograft model

This study proposes a combination method of using 3,4-dihydorxy-l-phenylalanine (DOPA) conjugated heparin (heparin-DOPA) and a low dose of anti-CD154 monoclonal antibody (MR-1) treatment to improve the survival time of intrahepatic islet xenograft. To inhibit instant blood mediated inflammatory reactions, heparin-DOPA was directly grafted to the pancreatic islet surface. The surface coverage of heparin-DOPA, the viability and functionality of heparin-DOPA grafted islets were evaluated. In addition, the combined effect of grafted heparin-DOPA and a low dose of MR-1 (a T-cell targeting immunosuppressive drug) on the survival of islet was evaluated in a xenograft model. Both unmodified islets and heparin-DOPA grafted islets were completely rejected within 2 weeks after intraportal transplantation. However, when 0.1 mg/mouse of MR-1 was administered (at day 0, 2, 4, 6 of transplantation) to 11 mice that had heparin-DOPA grafted islets transplanted to, seven out of the recipients maintained normoglycemia over 60 days. Therefore, we propose that a developed combinatory immunoprotection protocol of surface modification of pancreatic islets using heparin-DOPA with a low dose of MR-1 can be effective in prolonging the survival rate of transplanted islets in a xenograft model.     

Prolongation of intrasplenic islet xenograft survival

The spleen has been examined as a possible site for transplantation of rat islets into diabetic mice. Marked prolongation of islet xenograft survival in the spleen can be achieved with in vitro culture (24 C) and a single injection of either rabbit antiserum to mouse lymphocytes (MALS) alone or MALS and rabbit antiserum to rat lymphocytes (RALS) into the recipients. The percentage of survival of intrasplenic xenografts at 100 days was 16%, as compared with 70% when rat islet xenografts were transplanted via the portal vein. Further improvement in pretreatment regimens will be needed before the spleen can be used as an effective site for possible future islet allograft or xenograft transplants in man.     

Decomplementation with cobra venom factor prolongs survival of xenografted islets in a rat to mouse model

Although the involvement of complement in hyperacute rejection of xenotransplants is well recognized, its role in rejection of devascularized xenografts, such as pancreatic islets, is not completely understood. In this study, we investigated whether complement participates in the immunopathology of xeno-islet transplantation in a concordant rat to mouse model. Rat pancreatic islets were implanted under the kidney capsule of normal and cobra venom factor (CVF)-decomplementized diabetic C57BL/6 mice. Graft survival was monitored by blood glucose levels. Deposition of IgM and C3 on grafted islets in vivo or on isolated islets in vitro (after incubation with normal and decomplementized mouse serum), as well as CD4- and CD8-positive leucocyte infiltration of grafts, was checked by immunohistochemistry. In addition, complement-mediated cytotoxicity on rat islet cells was evaluated by a 3-(4, 5-dimethythiazolyl)-2.5-diphenyl-2H-tetrazolium-bromide (MTT) assay. A significant C3 deposition was found on grafted islets from the first day after transplantation in vivo, as well as on isolated islets after incubation with mouse serum in vitro. By MTT assay, complement-mediated cytotoxicity for islet cells was found. Decomplementation by CVF decreased C3 deposition on either isolated or grafted islets, delayed CD4- and CD8-positive leucocyte infiltration, led to significant inhibition of complement-mediated cytotoxicity for islet cells, and prolonged graft survival (mean survival time 21.3 versus 8.5 days; P<0.01). Our results indicate that decomplementation can prolong the survival time of devascularized xenografts across concordant species. The deposition of complement on transplanted islets may contribute to xenograft rejection by direct cytotoxicity and by promoting leucocyte infiltration.     

Magnetic resonance imaging of gadolinium-labeled pancreatic islets for experimental transplantation

New imaging techniques that couple anatomical resolution to sensitivity may greatly contribute to improving islet transplantation. In the present work, a report is given of the direct detection of islets by magnetic resonance imaging (MRI) after ex vivo cell labeling with the MRI T(1) contrast agent GdHPDO3A. Experiments on mouse and human islets demonstrated well-tolerated uptake of GdHPDO3A, based on morphology, viability, glucose-dependent insulin response and apoptosis/toxicity gene array profile. GdHPDO3A loading was sufficient for in vitro MRI cell detection. In vivo isotransplanted mouse islets into the kidney capsule and xenotransplanted human islets within the mouse liver were detected. Imaging specificity was supported by the absence of signal in unlabeled islet transplants, its persistence upon using fat-suppression MRI protocols and the colocalization with the transplanted islets. In conclusion, direct islet imaging with high spatial and contrast resolution after labeling with GdHPDO3A is demonstrated, allowing visualization of kidney subcapsular mouse islet grafts and intrahepatic human islet xenografts.     

糖尿病小鼠理想的胰岛移植部位

背景：胰岛移植到糖尿病小鼠不同部位影响胰岛移植成功率。 目的：比较糖尿病小鼠小网膜、肾被膜和腋窝3个部位胰岛移植效果,探索一个更理想的移植部位。 方法：应用淋巴细胞分离液分离纯化BALB/c小鼠胰岛;将胰岛移植到造模成功的糖尿病C57BL/6小鼠,按照不同的移植部位小网膜、肾被膜和腋窝进行对比观察。 结果与结论：分离纯化后获得高纯度胰岛,每只供体可获得胰岛(102±4)个,并具有良好生物活性;胰岛移植到糖尿病小鼠小网膜、肾被膜和腋窝3个部位后,均能降低血糖至正常范围,移植到小网膜与肾被膜的血糖值差异无显著性意义(P > 0.05),但均低于腋窝血糖值(P < 0.05)。移植后第7天,苏木精-伊红染色见小网膜部位移植胰岛形态基本完整,肾被膜部位移植胰岛形态不规则,腋窝部位移植物胰岛完全被破坏,伴炎症细胞浸润,小网膜和肾被膜降血糖效果优于腋窝。说明小网膜血供充足容量大,能够接纳较大体积的移植物,可能作为胰岛移植的理想部位。