微囊化犬和大鼠胰岛异种移植到链脲佐菌素诱导的糖尿病小鼠和非肥胖糖尿病（NOD）小鼠体内。

Microencapsulated dog and rat islet xenografts into streptozotocin-diabetic and NOD mice.

作者信息

Weber C J, Zabinsi S, Koschitzky T, Rajotte R, Wicker L, Peterson L, D'Agati V, Reemtsma K

机构信息

Luis A. Noboa Laboratory of Surgical Research, Department of Surgery, College of Physicians and Surgeons, Columbia University, New York, N.Y.

出版信息

Horm Metab Res Suppl. 1990;25:219-26.

PMID:2088974

Abstract

Microencapsulation is an appealing method for islet xenografting. However, graft failure has been related to a cellular reaction, particularly intense in spontaneously diabetic, NOD mice. The goal of this study was to characterize this reaction. Poly-l-lysine-alginate microcapsules containing dog or rat islets were xenografted intraperitoneally into streptozotocin (SZN)-diabetic C57BL/6J and spontaneously diabetic NOD mice, with or without recipient treatment with GK 1.5 (anti-CD4 monoclonal antibody). Both dog and rat islets in microcapsules normalized blood glucose (BG) routinely in both SZN and NOD mice within 24 hours. Empty microcapsules and GK 1.5 treatment did not affect BG. NODs destroyed both microencapsulated dog and rat islets more rapidly than did SZN-diabetic mice (P less than 0.01). Graft biopsies showed an intense cellular reaction and no viable islets. GK 1.5 treatment significantly prolonged both dog-to-NOD and rat-to-NOD grafts (P less than 0.01). Biopsies of long-term functioning grafts (on days #70-#95) demonstrated viable islets and no cellular reaction. In prediabetic NODs, encapsulated dog and rat islets elicited a moderate cellular reaction. Empty microcapsules excited no cellular reaction in either diabetic or prediabetic NODs.

摘要

微囊化是胰岛异种移植的一种有吸引力的方法。然而，移植失败与细胞反应有关，在自发性糖尿病的非肥胖糖尿病（NOD）小鼠中这种反应尤为强烈。本研究的目的是对这种反应进行表征。将含有犬或大鼠胰岛的聚-L-赖氨酸-海藻酸盐微囊经腹腔异种移植到链脲佐菌素（SZN）诱导糖尿病的C57BL/6J小鼠和自发性糖尿病的NOD小鼠体内，受体小鼠接受或不接受GK 1.5（抗CD4单克隆抗体）治疗。微囊中的犬和大鼠胰岛通常在24小时内使SZN和NOD小鼠的血糖（BG）恢复正常。空微囊和GK 1.5治疗对BG无影响。与SZN糖尿病小鼠相比，NOD小鼠更快地破坏了微囊化的犬和大鼠胰岛（P小于0.01）。移植组织活检显示有强烈的细胞反应且无存活的胰岛。GK 1.5治疗显著延长了犬到NOD和大鼠到NOD的移植存活时间（P小于0.01）。长期功能正常的移植组织（第70 - 95天）活检显示有存活的胰岛且无细胞反应。在糖尿病前期的NOD小鼠中，包封的犬和大鼠胰岛引发了中度的细胞反应。空微囊在糖尿病或糖尿病前期的NOD小鼠中均未引发细胞反应。