Reintgen D, Feldman J, Vervaert C, Seigler H F
Ann Surg. 1980 Jan;191(1):105-13. doi: 10.1097/00000658-198001000-00019.
Syrian hamsters were rendered diabetic with intraperitoneal streptozotocin and were maintained in the diabetic state for a minimum of 14 days. A hamster islet cell tumor was transplanted subcutaneously with a prompt return of water intake (38 +/- 9.1 ml/day to 7.1 +/- 2.2 ml/day, mean +/- SD), urine glucose (4.8 +/- 0.84 g/day to less than 250 mg/day), urine output (37.4 +/- 10.9 ml/day to 7.6 +/- 2.1 ml/day), blood glucose (297 +/- 31.9 mg/dl to 87.6 +/- 28 mg/dl), and weight gain (1.0 to 0.8 g/day) to normal control levels. Histologic examination of the engrafted tumors revealed a well encapsulated tumor with no evidence of metastatic disease. The transplanted insulinomas maintained well differentiated histologic features without evidence of necrosis. Immunopathologic studies failed to reveal any evidence of either humoral or cell mediated immunity directed toward the allograft. Each animal was successfully transplanted with a 1 mm tumor explant. A single rodent tumor donor provided adequate material for engraftment for five recipients. The transplanted insulinomas maintained full functional and enzymatic capabilities. Similar studies utilizing the hamster insulinoma engrafted into the athymic nude mouse showed amelioration of the same diabetic symptomatology. Many of the technical difficulties encountered with whole organ and isolated islet transplantation encourages development of a more practical model. These experimental results suggest an alternative method for supplying the diabetic with an endogenous insulin source.
将叙利亚仓鼠通过腹腔注射链脲佐菌素诱导成糖尿病,并使其维持糖尿病状态至少14天。将仓鼠胰岛细胞瘤皮下移植后,水摄入量迅速恢复(从38±9.1毫升/天降至7.1±2.2毫升/天,平均值±标准差),尿糖(从4.8±0.84克/天降至低于250毫克/天),尿量(从37.4±10.9毫升/天降至7.6±2.1毫升/天),血糖(从297±31.9毫克/分升降至87.6±28毫克/分升),体重增加(从每天1.0克增至0.8克)至正常对照水平。对移植肿瘤的组织学检查显示肿瘤包膜完整,无转移疾病迹象。移植的胰岛素瘤保持良好的分化组织学特征,无坏死迹象。免疫病理学研究未发现针对同种异体移植的体液或细胞介导免疫的任何证据。每只动物均成功移植了1毫米的肿瘤外植体。单个啮齿动物肿瘤供体提供的材料足以供5只受体移植。移植的胰岛素瘤保持了完整的功能和酶活性。利用移植到无胸腺裸鼠体内的仓鼠胰岛素瘤进行的类似研究显示,同样的糖尿病症状得到了改善。全器官和分离胰岛移植中遇到的许多技术难题促使人们开发一种更实用的模型。这些实验结果提示了一种为糖尿病患者提供内源性胰岛素来源的替代方法。