胰岛移植治疗胰腺移植术后移植物失功3例

目的 探讨胰岛移植治疗胰腺移植术后移植物失功的安全性及有效性,并总结文献经验。方法 回顾性分析中山大学附属第一医院3例胰岛移植治疗胰腺移植术后移植物失功的临床资料,并随访6个月进行总结分析。结果 胰腺移植术后移植物失功接受胰岛移植的3例患者术后胰岛功能良好,空腹C肽水平均较术前明显提升,出院前1例实现停用外源性胰岛素,其余2例胰岛素用量减少2/3以上,且均血糖平稳。结论 对胰腺移植术后移植物失功的患者实施胰岛移植可以有效地补救性治疗糖尿病,且安全性高。     

一种小鼠胰岛经门静脉肝内移植方法及疗效评价

目的 介绍一种糖尿病小鼠经门静脉到肝内胰岛移植的方法并进行移植前后的血糖、口服糖耐量、免疫组化等评价。方法 采用Balb/c小鼠,将分离纯化的小鼠胰岛培养6 h后,用自制的移植工具进行糖尿病模型小鼠的肝门静脉插管和输注胰岛,移植胰岛量为（320±30）IEQ,对移植前后的小鼠血糖进行测定,在移植后第10天进行糖耐量试验,并取受体小鼠肝脏,进行HE染色和免疫组化分析,观察胰岛细胞团在肝内的存活情况。结果受体小鼠胰岛移植后血糖均能长期维持正常,糖耐量试验结果显示与正常小鼠无统计学差异（P =0.81）,组织学结果显示胰岛细胞在小鼠肝内存活良好。结论 采用本方法可建立小鼠胰岛经门静脉移植到肝内的模型,为下一步进行胰岛移植相关药物筛选及免疫学等方面研究奠定了基础。     

大鼠胰岛移植物制备与异种移植

增加胰岛收获量，提高胰岛纯度一直是胰岛移植中面临的重要问题，本实验经胰管注射胶原酶，胰静止消化分离成年大鼠胰岛纯度一直是胰岛葡聚糖离心纯化。纯化后胰岛收获量为６１０－８２０个／胰纯度达９２％；胰岛形态结构完整，内分泌细胞超微结构保持良好，对葡萄糖刺激反应胰岛素释放量是基本分泌水平的８倍；异种移植可逆转实验性糖尿病小鼠的高血糖达一周。     

胰岛和胰岛干细胞的微创移植

目前 ,I型糖尿病的常规治疗方法是应用外源性胰岛素注射控制血糖。胰岛素注射不能完全控制血糖和远期并发症 ,因为常有血糖波动和低血糖发生 ,而且患者难免遭受注射所带来的不便和痛苦。全胰腺移植始于 2 0世纪 6 0年代初期 ,到 2 0 0 0年全球实施了近 1 0 0 0例手术[1 ] ,虽然患者移植后 1年生存率和移植功能存活率逐渐提高 ,但胰腺单独移植存活率低 ,只有与肾或其它脏器联合移植才能获得较高的成活率[2 ,3 ] 。尽管胰腺移植是一种有效的治疗方法 ,但要求条件高 ,损伤大 ,费用高 ,而且只有少数单位能够承担此项工作 ,难以普及。另外 ,还受…     

胰岛移植进展

近年来 ,随着胰岛分离、纯化技术的不断改进以及新型免疫抑制剂的问世和应用 ,临床同种胰岛移植已取得令人瞩目的进展[1 2 ] ,有可能在今后数年内得以广泛开展。本文对这些方面的进展作一综述。一、国际胰岛移植登记处的报告据国际胰岛移植登记处 (ITR)最近公布的结果 ,截止到2 0 0 0年 12月 31日 ,全球共有 5 1个研究中心开展了 4 93例成人胰岛移植 ,术后不依赖胰岛素的持续时间超过 12、2 4、36和 4 8个月的例数分别为 4 0、2 2、11和 6例。自体胰岛移植后停用胰岛素最长者已达 13年 ;Ⅰ型糖尿病 (IDDM )患者同种异体胰岛移植后停用胰…     

胰岛移植早期血糖控制对大鼠胰岛移植效果的影响

目的　探讨胰岛移植早期血糖控制对大鼠胰岛移植效果的影响。方法　体外实验 :将新鲜制备的SD大鼠胰岛在 4种不同糖浓度中培养 5d后恢复至常规糖浓度中培养 3d ,观察其形态、存活时间及功能变化。胰岛移植实验 :将糖尿病SD大鼠随机分为 3组 :移植及胰岛素控血糖组 ;单纯移植组和未移植 (对照 )组。监测各组的血糖水平。结果　在体外 ,短期的高糖培养对SD大鼠胰岛的形态、存活时间无明显影响 ,但可降低其对高糖刺激的反应能力。在糖浓度恢复正常后 ,该功能可恢复。移植实验中 ,血糖控制组在移植后 14d时 ,受体鼠血糖 ( 2 7.0± 4.0 )mmol/L与对照组 ( 3 3 .1± 1.8)mmol/L间差异有显著性 (P <0 .0 5 ) ,而单纯移植组与对照组的血糖差异仅维持到移植后 8d。结论　移植早期的血糖控制有改善胰岛移植效果的作用。     

Rapid loss of intraportally transplanted islets: an overview of pathophysiology and preventive strategies

Islets isolated from multiple pancreas donors are often necessary to achieve euglycemia in type 1 diabetic patients treated by islet allotransplantation. This increases the burden on the limited pool of donor organs. After infusion into the portal vein, a substantial percentage of islets are lost in the immediate post-transplant period through an inflammatory response termed the instant blood-mediated inflammatory reaction (IBMIR). IBMIR is equally, if not more of a problem after islet xenotransplantation, e.g., using pig islets in non-human primates. Coagulation, platelet aggregation, complement activation, and neutrophil and monocyte infiltration play roles in this reaction. IBMIR is potentially triggered by islet surface molecules, such as tissue factor and collagen residues that are normally not in direct contact with the blood. Also, stress during the islet isolation process results in the expression and production of several inflammatory mediators by the islets themselves. The potential mechanisms involved in this rapid graft loss and treatment options to reduce this loss are reviewed. Preventive strategies for IBMIR can include systemic treatment of the recipient, pre-conditioning of the isolated islets, or, in the case of xenotransplantation, genetic modification of the organ-source pig. Pre-conditioning of islets in culture by exposure to anti-inflammatory agents or by genetic modification harbors fewer risks of systemic complications in the recipient. The future of clinical islet transplantation will, at least in part, depend on the success of efforts made to reduce rapid graft loss, and thus allow islet transplantation to become a more efficient therapy by the use of single donors.     

Hyperoxia improves the survival of intraportally transplanted syngeneic pancreatic islets

BACKGROUND: Hypoxia in the portal vein may compromise the survival of intraportally transplanted pancreatic islets. We therefore examined the effect of inspired oxygen on the outcome of islet transplantation. METHODS: Blood glucose concentrations, glucose tolerance, and the size and number of surviving islets were measured in diabetic rats housed for 48 hr under hyperoxic (100% O(2)), hypoxic (11% O(2)), or normoxic (21%O(2)) conditions after intraportal transplantation of 350, 500, 700, or 1,000 syngeneic islets. RESULTS: In normoxic diabetic rats, the smallest graft size to consistently restore normoglycemia was 1,000 islets. A graft size of 700 islets was effective in only three of nine animals, whereas 500 islets were ineffective in all eight animals undergoing transplantation. In contrast, in hyperoxically housed rats, graft sizes of 700 or 500 islets restored normoglycemia in eight of nine or five of eight animals, respectively. In those animals that became normoglycemic, the glucose tolerance of the hyperoxically treated rats receiving 700 islets was almost identical to that of normoxically housed animals receiving 1,000 islets. The average size of the islets 6 weeks after transplantation was the same in livers of hyperoxic and control rats. However, the total islet area and number of islets engrafted in hyperoxic rats was significantly increased when compared with livers from normoxic animals receiving the same graft size, so the area in hyperoxic rats receiving 700 islets was not significantly different from normoxic recipients of 1,000 islets. CONCLUSIONS: Hyperoxia posttransplantation increases the number of islets that survive the engraftment process and allows normalization of plasma glucose levels with a smaller number of transplanted islets.     

Remaining experiences of living kidney donors more than 3 yr after early recipient graft loss

Living kidney donor programs, based on willingness among family members and close relatives to donate, have made it possible to perform a satisfactory number of kidney transplantations. Early graft loss in the recipient may occur and it is not known if such an event will result mainly in acute, rather transient, emotional reactions or if long-lasting reactions may be evoked in the living kidney donor. The aim of the present study was to assess and describe the remaining experiences of donors (n = 10) more than 3 yr after early recipient graft loss or death of the recipient. A phenomenographic, interview-based research approach was used. Five different fields or domains were identified: (i) the decision to donate; (ii) the information provided; (iii) care received at the time of donation; (iv) responses at graft failure; and (v) concerns remaining at the time of the interview. All donors expressed that they had volunteered to donate and that no stress had been put on them. The information given prior to and in connection with the donation procedure was deemed insufficient but all donors were satisfied with the medical care provided in connection with the nephrectomy and in the immediate post-operative period. Graft failure was immediately accepted on the intellectual level by nine of 10 donors but still evoked emotional reactions and responses included a wish that continuing contact with the transplant staff had been provided. The present interview-based study shows that it is of importance that the donor is thoroughly informed about all donor as well as recipient-related factors including the potential risk of recipient graft failure. In case of graft failure, or the death of the recipient, the transplant unit staff members should offer contact for discussions of medical matters as well as for psychosocial support. In individual cases it may be necessary to maintain such a supportive contact channel for a prolonged period of time.     

mPEG包裹大鼠胰岛在同种胰岛移植中的作用分析

目的探讨单甲氧基聚乙二醇(mPEG)对同种大鼠胰岛移植物存活的影响及作用机制。方法分离纯化Wistar大鼠胰岛,处理组胰岛用30%mPEG包裹,对照组不作处理,植入糖尿病SD大鼠的右后肢肌肉,空白对照组在相同部位注入生理盐水,动态监测血糖变化,病理切片检测移植物存活,通过淋巴细胞混合培养检测免疫排斥反应。结果mPEG包裹的胰岛存活时间明显延长[(75.8±4.5)d vs(7.2±1.1)d,P<0.05],免疫组化染色呈强阳性,对照组仅见少量阳性颗粒;处理组淋巴细胞刺激指数明显低于对照组[(1.27±0.22)vs(3.78±0.32),P<0.05)]。结论mPEG包裹大鼠胰岛可有效延长胰岛存活时间,其机制与免疫修饰作用有关。     

Effectiveness of hydroxyethyl starch (HES) on purification of pancreatic islets

BACKGROUND: The isolation of large-scale and high-quality islets from the pancreas is essential for a successful islet transplantation. We developed a hydroxyethyl starch (HES)-Collins solution as the purification medium and evaluated its usefulness on islet isolation from the pancreas of beagle dogs. MATERIALS AND METHODS: The pancreas of beagle dog was digested using our original 2-step automated technique. Islets were purified by discontinuous purification method on HES-Collins solution (group 1, n = 10) or Euro-Ficoll solution (group 2, n = 16) with a COBE2991 cell processor. Islet yield and purity, changes in islet number during 3-day cultures, static incubation, perifusion study, and insulin content were examined. In addition, the islets were autotransplanted into the liver via the portal vein. RESULTS: Although no significant differences were detected, yield and purity were higher in group 1. After 3 days of culture, the islet number decreased less in group 1. Both under static incubation and in the perifusion study, stimulation indices were 4.50 +/- 1.82 and 6.02 +/- 1.05, which were significantly higher than the 2.18 +/- 0.67 and 3.32 +/- 1.46 observed in group 2. Also, insulin content of the islets was significantly higher in group 1 than in group 2. Fasting blood glucose levels were maintained at values below 100 mg/dl for 100 days in group 1 and around 200 mg/dl in group 2. CONCLUSIONS: The use of HES-Collins solution was associated with an improvement of islet yield and purity. Also, islet viability and function were preserved longer during culture. Accordingly, islet purification using HES-Collins solution might be recommended for clinical islet transplantation.