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Characterization of a mouse model of islet transplantation using MIN-6 cells.
Islets ( IF 1.9 ) Pub Date : 2020-06-22 , DOI: 10.1080/19382014.2020.1763719
Douglas O Sobel 1 , Barath Ramasubramanian 1 , Larry Mitnaul 1
Affiliation  

Immortalized beta cells are an abundant source of insulin-producing cells. Although MIN-6 cells have similar characteristics as normal islets in vitro, the in vivo use of MIN-6 cells has not been fully described. This study characterizes in vivo mouse models of MIN-6 transplantation and rejection. Subcutaneous (sc) transplantation of MIN-6 cells in either Matrigel or HyStem-C hydrogels reduced blood sugars in nude mice and thus are good matrices for MIN-6 cells in vivo. NOD mice are good transplant recipients since they best rejected MIN-6 cells. MLR responses from BalbC, Black Webster, Swiss Black, C3H, and NOD mice correlated with mean blood glucose response suggesting the importance of allogeneic differences in the rejection of cells. Three days of cyclosporine administration caused no inhibition of MIN-6 cell rejection and 6 days resulted in a transient decrease in blood glucose, while daily administration inhibited rejection long term. Kinetic glucose tolerance (GTT) studies in nude mice demonstrated transplanted MIN-6 cells are close but not as effective as normal islets in controlling blood glucose and blood glucose set point for insulin release in MIN-6 cells decreases to hypoglycemic levels over time. To avoid hypoglycemia, the effect of MIN-6 cell irradiation was assessed. However, irradiation only delayed the development of hypoglycemia, not altering the final glucose set point for insulin release. In conclusion, we have characterized a mouse model for beta-cell transplantation using subcutaneous MIN-6 cells that can be used as a tool to study approaches to mitigate immune rejection.



中文翻译:

使用 MIN-6 细胞对小鼠胰岛移植模型进行表征。

永生化β细胞是产生胰岛素的细胞的丰富来源。尽管 MIN-6 细胞在体外具有与正常胰岛相似的特征,但尚未完全描述 MIN-6 细胞在体内的应用。这项研究表征了 MIN-6 移植和排斥的体内小鼠模型。在 Matrigel 或 HyStem-C 水凝胶中皮下 ( sc ) 移植 MIN-6 细胞可降低裸鼠的血糖,因此是体内MIN-6 细胞的良好基质. NOD 小鼠是良好的移植受体,因为它们最能排斥 MIN-6 细胞。BalbC、Black Webster、Swiss Black、C3H 和 NOD 小鼠的 MLR 反应与平均血糖反应相关,表明同种异体差异在细胞排斥中的重要性。3 天的环孢素给药对 MIN-6 细胞排斥没有抑制作用,6 天导致血糖暂时降低,而每天给药可长期抑制排斥反应。裸鼠的动力学葡萄糖耐量 (GTT) 研究表明,移植的 MIN-6 细胞在控制血糖方面与正常胰岛接近但不如正常胰岛有效,MIN-6 细胞中胰岛素释放的血糖设定点随时间降低至低血糖水平。为了避免低血糖,评估了 MIN-6 细胞照射的效果。然而,辐照只会延迟低血糖的发生,而不会改变胰岛素释放的最终葡萄糖设定点。总之,我们已经描述了一种使用皮下 MIN-6 细胞进行 β 细胞移植的小鼠模型,该模型可用作研究减轻免疫排斥的方法的工具。

更新日期:2020-06-22
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