Menger Maximilian M, Nalbach Lisa, Roma Leticia P, Körbel Christina, Wrublewsky Selina, Glanemann Matthias, Laschke Matthias W, Menger Michael D, Ampofo Emmanuel
Institute for Clinical and Experimental Surgery, Saarland University, Homburg/Saar, Germany.
Biophysics Department, Center for Human and Molecular Biology, Saarland University, Homburg/Saar, Germany.
Br J Pharmacol. 2020 Apr;177(7):1651-1665. doi: 10.1111/bph.14925. Epub 2020 Feb 10.
Pancreatic islet transplantation is a promising therapeutic approach for Type 1 diabetes. A major prerequisite for the survival of grafted islets is a rapid revascularization after transplantation. Erythropoietin (EPO), the primary regulator of erythropoiesis, has been shown to promote angiogenesis. Therefore, we investigated in this study whether EPO improves the revascularization of transplanted islets.
Islets from FVB/N mice were transplanted into dorsal skinfold chambers of recipient animals, which were daily treated with an intraperitoneal injection of EPO (500 IU·kg ) or vehicle (control) throughout an observation period of 14 days. In a second set of experiments, animals were only pretreated with EPO over a 6-day period prior to islet transplantation. The revascularization of the grafts was assessed by repetitive intravital fluorescence microscopy and immunohistochemistry. In addition, a streptozotocin-induced diabetic mouse model was used to study the effect of EPO-pretreatment on the endocrine function of the grafts.
EPO treatment slightly accelerated the revascularization of the islet grafts. This effect was markedly more pronounced in EPO-pretreated animals, resulting in significantly higher numbers of engrafted islets and an improved perfusion of endocrine tissue without affecting systemic haematocrit levels when compared with controls. Moreover, EPO-pretreatment significantly accelerated the recovery of normoglycaemia in diabetic mice after islet transplantation.
These findings demonstrate that, particularly, short-term EPO-pretreatment represents a promising therapeutic approach to improve the outcome of islet transplantation, without an increased risk of thromboembolic events.
胰岛移植是1型糖尿病一种很有前景的治疗方法。移植胰岛存活的一个主要前提是移植后快速血管再生。促红细胞生成素（EPO）是红细胞生成的主要调节因子，已被证明可促进血管生成。因此，我们在本研究中调查了EPO是否能改善移植胰岛的血管再生。
将FVB/N小鼠的胰岛移植到受体动物的背部皮褶腔中，在14天的观察期内，每天给受体动物腹腔注射EPO（500 IU·kg）或赋形剂（对照）。在另一组实验中，动物仅在胰岛移植前6天用EPO预处理。通过重复活体荧光显微镜检查和免疫组织化学评估移植物的血管再生情况。此外，使用链脲佐菌素诱导的糖尿病小鼠模型研究EPO预处理对移植物内分泌功能的影响。
EPO治疗轻微加速了胰岛移植物的血管再生。在EPO预处理的动物中，这种效果明显更显著，与对照组相比，移植的胰岛数量显著增加，内分泌组织灌注改善，且不影响全身血细胞比容水平。此外，EPO预处理显著加速了胰岛移植后糖尿病小鼠正常血糖的恢复。
这些发现表明，特别是短期EPO预处理是一种很有前景的治疗方法，可改善胰岛移植的结果，且不会增加血栓栓塞事件的风险。
