Takemoto Naohiro, Konagaya Shuhei, Kuwabara Rei, Iwata Hiroo
1 Department of Reparative Materials, Institute for Frontier Medical Sciences, Kyoto University, Shogoin, Sakyo-Ku, Kyoto, Japan.
Transplantation. 2015 May;99(5):942-7. doi: 10.1097/TP.0000000000000579.
Transplantation of islets of Langerhans (islets) has been investigated in the clinic to treat patients with insulin-dependent diabetes mellitus. Islet grafts have been maintained by administering immunosuppressive drugs, which can lead to complications in the long term. Alternatives to immunosuppressive therapy are eagerly desired. In this study, we examined the transplantation of coaggregates of CD4CD25 regulatory T (Treg) cells.
Coaggregates of Treg cells from C57BL/6 mice and islet cells from BALB/c mice were prepared on agarose hydrogel with small round-bottomed wells. Four hundred coaggregates were transplanted into the livers of streptozotocin-induced diabetic C57BL/6 mice without systemic immunosuppression.
The Treg cells and islet cells were distributed randomly in the coaggregates. When 400 coaggregates were transplanted into 9 C57BL/6 mice via the portal vein, 6 of the 9 recipients demonstrated blood glucose less than 250 mg/dL for more than 100 days. A number of insulin-positive cells were observed in the livers at 120 days after transplantation.
The Treg cells and islet cells were distributed randomly in the coaggregates. After intraportal transplantation of the coaggregates, Treg cells in the aggregates enabled the long-term survival of allogeneic islet cell grafts in the liver without the use of immunosuppressive drugs.
胰岛移植已在临床上用于治疗胰岛素依赖型糖尿病患者。胰岛移植一直通过使用免疫抑制药物来维持，但长期使用可能导致并发症。人们迫切需要免疫抑制治疗的替代方法。在本研究中，我们检测了CD4CD25调节性T（Treg）细胞共聚物的移植情况。
在带有小圆形底孔的琼脂糖水凝胶上制备C57BL/6小鼠的Treg细胞与BALB/c小鼠的胰岛细胞的共聚物。将400个共聚物移植到经链脲佐菌素诱导的糖尿病C57BL/6小鼠肝脏中，不进行全身免疫抑制。
Treg细胞和胰岛细胞在共聚物中随机分布。当通过门静脉将400个共聚物移植到9只C57BL/6小鼠体内时，9只受体中有6只在超过100天的时间里血糖低于250mg/dL。移植后120天在肝脏中观察到许多胰岛素阳性细胞。
Treg细胞和胰岛细胞在共聚物中随机分布。共聚物经门静脉移植后，共聚物中的Treg细胞能够使同种异体胰岛细胞移植物在肝脏中长期存活，而无需使用免疫抑制药物。
