Research and Development Center, Otsuka Pharmaceutical Factory, Inc., Naruto, Tokushima, Japan.
Xenotransplantation. 2017 Jul;24(4). doi: 10.1111/xen.12313. Epub 2017 May 16.
In patients with type 1 diabetes, allogeneic islet transplantation can provide normal HbA1c concentrations, but it requires immunosuppression. Transplanting encapsulated islets into the peritoneal cavity could reduce or eliminate the need for immunosuppression. One of the uncertain features of intraperitoneal islet transplantation is the difficulty of measuring C-peptide concentrations in peripheral blood, which is often used for the marker of islet function. We hypothesized that secreted C-peptide from intraperitoneally transplanted islets was mostly consumed in the peritoneal cavity, which resulted in low C-peptide concentrations in peripheral blood.
In each of two experiments, encapsulated neonatal porcine islets were intraperitoneally transplanted into four nude mice with streptozotocin-induced diabetes. Three diabetic nude mice without transplanted islets were used as diabetic controls, and three untreated healthy nude mice were used as normal controls. Islet functions were monitored for 2 months in the first experiment and 6 months in the second experiment. Encapsulated islets were retrieved after each experiment and evaluated by fluorescein diacetate/propidium iodide tests for the viability and static glucose-stimulated insulin release tests for the function. C-peptide concentrations from the blood and from the intraperitoneal cavity at 6 months were compared.
In both experiments, diabetes was reversed in all transplanted mice, and oral glucose tolerance test showed improved profiles. In general, retrieved islets were viable and functional. However, blood porcine C-peptide concentrations were low at both 2 and 6 months, and concentrations in the ascites of peritoneal cavity were 40 times as high as those in blood.
The peripheral blood sampling for c-peptide, though highly informative in vascularized grafts, may not be the primary tool for monitoring the health and function of encapsulated products when transplanted into intraperitoneal cavity. Our results might explain the clinical feature of the low C-peptide blood concentrations after successful intraperitoneal encapsulated islet transplantation.
在 1 型糖尿病患者中，同种异体胰岛移植可以提供正常的 HbA1c 浓度，但需要免疫抑制。将包封的胰岛移植到腹腔内可以减少或消除对免疫抑制的需求。腹腔内胰岛移植的一个不确定特征是外周血中 C 肽浓度的测量困难，C 肽通常用作胰岛功能的标志物。我们假设从腹腔内移植的胰岛分泌的 C 肽大部分在腹腔内被消耗，导致外周血中 C 肽浓度较低。
在两项实验中的每一项中，将包封的新生猪胰岛移植到四只因链脲佐菌素诱导糖尿病的裸鼠的腹腔内。未移植胰岛的三只糖尿病裸鼠作为糖尿病对照组，三只未处理的健康裸鼠作为正常对照组。在第一项实验中监测胰岛功能 2 个月，在第二项实验中监测 6 个月。在每次实验后回收包封的胰岛，并通过荧光素二乙酸/碘化丙啶试验评估其活力和静态葡萄糖刺激胰岛素释放试验评估其功能。比较 6 个月时血液和腹腔内的 C 肽浓度。
在两项实验中，所有移植的小鼠的糖尿病均得到逆转，口服葡萄糖耐量试验显示改善的曲线。一般来说，回收的胰岛是有活力和功能的。然而，血液中的猪 C 肽浓度在 2 个月和 6 个月时都很低，腹腔内腹水的浓度是血液的 40 倍。
尽管在外周血管化移植物中，C 肽的外周血取样非常有信息价值，但当移植到腹腔内时，它可能不是监测包封产品健康和功能的主要工具。我们的结果可能解释了成功的腹腔内包封胰岛移植后 C 肽血浓度较低的临床特征。
