Mamujee S N, Zhou D, Wheeler M B, Vacek I, Sun A M
Department of Physiology, Faculty of Medicine, University of Toronto, Ontario, Canada.
Ann Transplant. 1997;2(3):27-32.
To evaluate the growth and insulin secretion from microencapsulated beta TC6-F7 cells in vitro and to assess the in vivo function of microencapsulated cells transplanted in rats with steptozotocin (STZ)-induced diabetes.
Alginate-poly-L-lysine encapsulated beta TC6-F7 cells were exposed to glucose, isobutylmethylxanthine (IBMX) and glucagon-like peptide I (7-36 amide) in a static in vitro challenge. In vivo, 2.5-3.5 x 10(7) encapsulated cells were implanted into diabetic rats. Graft function was evaluated by monitoring blood glucose concentrations and by an intraperitoneal glucose tolerance test.
The cell density (number of cells per capsule) of cultured microencapsulated beta TC6-F7 cells increased almost 35-fold over a 55 day observation period to reach a plateau of approximately 3500 cells/capsule. While insulin secretion per capsule remained unchanged over the first 21 days of culture, a 7-fold increase was observed during the last 14 days of the 55 day observation period. Intraperitoneal transplantation of 3.5 x 10(7) encapsulated cells into diabetic rats resulted, within 24 hours, in reversal of hyperglycemia for up to 60 days. Post-transplantation blood glucose concentrations varied between 2 and 4 mM. Glucose clearance rates evaluated by an intraperitoneal glucose tolerance test at 30 days post-transplantation resulted in a markedly flat glucose clearance curve with blood glucose never rising above 4 mM. The glucose challenge of microencapsulated cells recovered 30 days post-transplantation resulted in a 2-fold increase in insulin response at glucose concentrations greater than 5.5 mM as compared to glucose-free media. In addition, immunostaining of recovered grafted tissue for insulin, reveals a strong presence of the peptide within the cell population.
These data demonstrate the potential use of an immunoisolated beta-cell line for the treatment of diabetes.
评估微囊化βTC6 - F7细胞在体外的生长及胰岛素分泌情况，并评估移植于链脲佐菌素（STZ）诱导糖尿病大鼠体内的微囊化细胞的功能。
在静态体外刺激实验中，将海藻酸钠 - 聚-L - 赖氨酸包裹的βTC6 - F7细胞暴露于葡萄糖、异丁基甲基黄嘌呤（IBMX）和胰高血糖素样肽I（7 - 36酰胺）中。在体内实验中，将2.5 - 3.5×10⁷个包裹细胞植入糖尿病大鼠体内。通过监测血糖浓度和进行腹腔葡萄糖耐量试验来评估移植物功能。
在55天的观察期内，培养的微囊化βTC6 - F7细胞的细胞密度（每胶囊细胞数）增加了近35倍，达到约3500个细胞/胶囊的平台期。虽然在培养的前21天每胶囊胰岛素分泌保持不变，但在55天观察期的最后14天观察到增加了7倍。将3.5×10⁷个包裹细胞腹腔移植到糖尿病大鼠体内，在24小时内导致高血糖症逆转长达60天。移植后血糖浓度在2至4 mM之间变化。移植后30天通过腹腔葡萄糖耐量试验评估的葡萄糖清除率导致葡萄糖清除曲线明显平坦，血糖从未升至4 mM以上。移植后30天回收的微囊化细胞的葡萄糖刺激导致在葡萄糖浓度大于5.5 mM时胰岛素反应比无葡萄糖培养基增加了2倍。此外，回收的移植组织的胰岛素免疫染色显示细胞群体中强烈存在该肽。
这些数据证明了免疫隔离的β细胞系在糖尿病治疗中的潜在用途。
