Black Sasha P, Constantinidis Ioannis, Cui Hong, Tucker-Burden Carol, Weber Collin J, Safley Susan A
Charles River Laboratories, Pre-clinical Services Montreal, Senneville, Que., Canada H9X 3R3.
Biochem Biophys Res Commun. 2006 Feb 3;340(1):236-43. doi: 10.1016/j.bbrc.2005.11.180. Epub 2005 Dec 9.
Our goal is to develop effective islet grafts for treating type 1 diabetes. Since human islets are scarce, we evaluated the efficacy of a microencapsulated insulin-secreting conditionally transformed allogeneic beta-cell line (betaTC-tet) in non-obese diabetic mice treated with tetracycline to inhibit cell growth. Relatively low serum levels of tetracycline controlled proliferation of betaTC-tet cells without inhibiting effective control of hyperglycemia in recipients. There was no significant host cellular reaction to the allografts or host cell adherence to microcapsules, and host cytokine levels were similar to those of sham-operated controls. We conclude that encapsulated allogeneic beta-cell lines may be clinically relevant, because they effectively restore euglycemia and do not elicit a strong cellular immune response following transplantation. To our knowledge, this is the first extensive characterization of the kinetics of host cellular and cytokine responses to an encapsulated islet cell line in an animal model of type 1 diabetes.
我们的目标是开发用于治疗1型糖尿病的有效胰岛移植体。由于人类胰岛稀缺，我们评估了微囊化的胰岛素分泌条件性转化同种异体β细胞系（betaTC-tet）在接受四环素治疗以抑制细胞生长的非肥胖糖尿病小鼠中的疗效。相对较低的血清四环素水平可控制betaTC-tet细胞的增殖，同时又不会抑制受体对高血糖的有效控制。宿主对同种异体移植物没有明显的细胞反应，宿主细胞也不会黏附到微囊上，并且宿主细胞因子水平与假手术对照组相似。我们得出结论，封装的同种异体β细胞系可能具有临床相关性，因为它们能有效恢复正常血糖水平，且移植后不会引发强烈的细胞免疫反应。据我们所知，这是在1型糖尿病动物模型中首次对宿主细胞和细胞因子对封装胰岛细胞系反应动力学进行的广泛表征。
