Elliott Robert B, Escobar Livia, Tan Paul L J, Muzina Maria, Zwain Sahar, Buchanan Christina
Living Cell Technologies, Aukland, New Zealand.
Xenotransplantation. 2007 Mar;14(2):157-61. doi: 10.1111/j.1399-3089.2007.00384.x.
The long-term viability and function of transplanted encapsulated neonatal porcine islets was examined in a diabetic patient.
A 41-yr-old Caucasian male with type 1 diabetes for 18 yr was given an intraperitoneal transplant of alginate-encapsulated porcine islets at the dose of 15,000 islet equivalents (IEQs)/kg bodyweight (total dose 1,305,000 IEQs) via laparoscopy. By 12 weeks following the transplant, his insulin dose was significantly reduced by 30% (P = 0.0001 by multiple regression tests) from 53 units daily prior to transplant. The insulin dose returned to the pre-transplant level at week 49. Improvement in glycaemic control continued as reflected by total glycated haemoglobin of 7.8% at 14 months from a pre-transplant level of 9.3%. Urinary porcine C-peptide peaked at 4 months (9.5 ng/ml) and remained detectable for 11 months (0.6 ng/ml). The patient was followed as part of a long-term microbiologic monitoring programme which subsequently showed no evidence of porcine viral or retroviral infection. At laparoscopy 9.5 yr after transplantation, abundant nodules were seen throughout the peritoneum. Biopsies of the nodules showed opacified capsules containing cell clusters that stained as live cells under fluorescence microscopy. Immunohistology noted sparse insulin and moderate glucagon staining cells. The retrieved capsules produced a small amount of insulin when placed in high glucose concentrations in vitro. An oral glucose tolerance test induced a small rise in serum of immuno-reactive insulin, identified as porcine by reversed phase high pressure liquid chromatography.
This form of xenotransplantation treatment has the potential for sustained benefit in human type 1 diabetics.
在一名糖尿病患者中检测了移植的封装新生猪胰岛的长期存活能力和功能。
一名41岁、患1型糖尿病18年的白种男性通过腹腔镜接受了腹腔内移植海藻酸盐封装的猪胰岛,剂量为15,000胰岛当量(IEQs)/千克体重(总剂量1,305,000 IEQs)。移植后12周,他的胰岛素剂量从移植前每日53单位显著降低了30%(多元回归测试P = 0.0001)。胰岛素剂量在第49周恢复到移植前水平。糖化血红蛋白总量从移植前的9.3%降至14个月时的7.8%,这反映出血糖控制持续改善。尿猪C肽在4个月时达到峰值(9.5 ng/ml),并在11个月内可检测到(0.6 ng/ml)。该患者作为长期微生物监测项目的一部分接受随访,随后未发现猪病毒或逆转录病毒感染的证据。移植9.5年后进行腹腔镜检查时,整个腹膜可见大量结节。结节活检显示不透明的胶囊内含有细胞簇,在荧光显微镜下染色为活细胞。免疫组织学检查发现胰岛素染色稀疏,胰高血糖素染色中等。回收的胶囊在体外置于高葡萄糖浓度中时产生少量胰岛素。口服葡萄糖耐量试验诱导免疫反应性胰岛素血清小幅升高,通过反相高压液相色谱法鉴定为猪胰岛素。
这种异种移植治疗形式对人类1型糖尿病患者有持续获益的潜力。