Though cell transplantation is becoming an attractive therapeutic method, uncontrolled cell proliferation or overexpression of cellular functions could cause adverse effects. These unfavorable outcomes could be avoided by regulating the proliferation or functioning of transplanted cells. In this study, we used a combination of the herpes simplex virus thymidine kinase (HSVtk) gene, a suicide gene, and ganciclovir (GCV) to control the proliferation and functioning of insulin-secreting cells after transplantation in diabetic mice. Mouse pancreatic β cell line MIN6 cells were selected as insulin-secreting cells for transfection with the HSVtk gene to obtain MIN6/HSVtk cells. Proliferation of MIN6/HSVtk cells was suppressed by GCV in a concentration-dependent manner; 0.25 μg/mL GCV maintained a constant number of MIN6/HSVtk cells for at least 16 days. MIN6 or MIN6/HSVtk cells were then transplanted to streptozotocin-induced diabetic mice. Mice transplanted with MIN6 cells exhibited hypoglycemia irrespective of GCV administration. In contrast, normal (around 150 mg/dL) blood glucose levels were maintained in mice transplanted with MIN6/HSVtk cells by a daily administration of 50 mg/kg of GCV. These results indicate that controlling the proliferation and functioning of HSVtk gene-expressing cells by GCV could greatly improve the usefulness and safety of cell-based therapy.

尽管细胞移植正在成为一种有吸引力的治疗方法，但是不受控制的细胞增殖或细胞功能的过度表达可能会引起不利影响。通过调节移植细胞的增殖或功能可以避免这些不利的结果。在这项研究中，我们使用单纯疱疹病毒胸苷激酶（HSVtk）基因，自杀基因和更昔洛韦（GCV）的组合来控制糖尿病小鼠移植后胰岛素分泌细胞的增殖和功能。选择小鼠胰腺β细胞系MIN6细胞作为胰岛素分泌细胞，用HSVtk基因转染以获得MIN6 / HSVtk细胞。MIN6 / HSVtk细胞的增殖受到浓度依赖性的GCV抑制。0.25μg/ mL GCV至少在16天内保持恒定数量的MIN6 / HSVtk细胞。然后将MIN6或MIN6 / HSVtk细胞移植到链脲佐菌素诱导的糖尿病小鼠中。不论是否使用GCV，移植有MIN6细胞的小鼠均表现出低血糖。相反，通过每天施用50 mg / kg的GCV，在移植了MIN6 / HSVtk细胞的小鼠中，血糖水平保持正常（约150 mg / dL）。这些结果表明，通过GCV控制表达HSVtk基因的细胞的增殖和功能可以大大提高基于细胞的疗法的实用性和安全性。通过每天施用50 mg / kg的GCV，在移植了MIN6 / HSVtk细胞的小鼠中维持正常（约150 mg / dL）的血糖水平。这些结果表明，通过GCV控制表达HSVtk基因的细胞的增殖和功能可以大大提高基于细胞的疗法的实用性和安全性。通过每天施用50 mg / kg的GCV，在移植了MIN6 / HSVtk细胞的小鼠中维持正常（约150 mg / dL）的血糖水平。这些结果表明，通过GCV控制表达HSVtk基因的细胞的增殖和功能可以大大提高基于细胞的疗法的实用性和安全性。