Wennberg L, Song Z, Bennet W, Zhang J, Nava S, Sundberg B, Bari S, Groth C G, Korsgren O
Department of Transplantation Surgery, Karolinska Institute, Huddinge Hospital, Stockholm, Sweden.
Transplantation. 2001 Apr 27;71(8):1024-33. doi: 10.1097/00007890-200104270-00002.
Transplantation of adult porcine islets (APIs) offers a possible means of treating diabetes. However, isolating APIs has been notoriously difficult. Furthermore, islet xenograft rejection must be prevented.
APIs were isolated by a modified automated method. API quality was assessed by static glucose stimulation (SGS), by transplantation to diabetic nude mice and by intraperitoneal glucose tolerance tests (IPGTTs). The morphologic characteristics of API xenograft rejection in rats were studied immunohistochemically. Furthermore, APIs were transplanted to diabetic rats that were either left untreated or immunosuppressed with cyclosporine A (CsA), mycophenolate mofetil (MMF) and leflunomide (LEF). B-glucose and porcine C-peptide levels were monitored and grafts were studied morphologically.
Large numbers of APIs were isolated. At SGS, insulin release increased significantly. All nude mice transplanted with APIs were normoglycemic within 24 hr and remained so for up to 1 year. During IPGTTs, B-glucose levels were rapidly regulated to porcine levels. In untreated rats, API xenografts were destroyed within 6 days by a cellular infiltrate consisting mainly of macrophages. In untreated diabetic rats normoglycemia was sustained for 5.5+/-0.3 days. Rats immunosuppressed with CsA+MMF+LEF remained normoglycemic for 59.6+/-11.3 days. In 3 of 11 rats, normoglycemia was sustained for up to 101 days. Porcine C-peptide was detected in serum. At recurrence of hyperglycemia, many mononuclear cells were found close to the xenografts. However, only occasional cells infiltrated the grafts and many APIs were intact.
Well-functioning APIs can be isolated in large numbers. API xenografts can be protected from rejection and can maintain an adequate function for up to 100 days, in rats immunosuppressed with CsA+MMF+LEF.
成年猪胰岛（API）移植为治疗糖尿病提供了一种可能的方法。然而，分离API一直非常困难。此外，必须防止胰岛异种移植排斥反应。
采用改良的自动化方法分离API。通过静态葡萄糖刺激（SGS）、移植到糖尿病裸鼠以及腹腔内葡萄糖耐量试验（IPGTT）评估API质量。采用免疫组织化学方法研究大鼠API异种移植排斥反应的形态学特征。此外，将API移植到未治疗或用环孢素A（CsA）、霉酚酸酯（MMF）和来氟米特（LEF）免疫抑制的糖尿病大鼠体内。监测β-葡萄糖和猪C肽水平，并对移植物进行形态学研究。
分离出大量的API。在SGS时，胰岛素释放显著增加。所有移植了API的裸鼠在24小时内血糖正常，并维持长达1年。在IPGTT期间，β-葡萄糖水平迅速调节至猪的水平。在未治疗的大鼠中，API异种移植物在6天内被主要由巨噬细胞组成的细胞浸润破坏。在未治疗的糖尿病大鼠中，血糖正常持续5.5±0.3天。用CsA+MMF+LEF免疫抑制的大鼠血糖正常持续59.6±11.3天。在11只大鼠中的3只，血糖正常持续长达101天。血清中检测到猪C肽。在血糖再次升高时，在异种移植物附近发现许多单核细胞。然而，只有偶尔的细胞浸润移植物，许多API保持完整。
可以大量分离功能良好的API。在用CsA+MMF+LEF免疫抑制的大鼠中，API异种移植物可以免受排斥反应的影响，并能维持足够的功能长达100天。
