Few studies have examined the differentiation of human embryonic stem cell (hESC)-derived pancreatic endoderm cells (PECs) in different implantation sites. Here, we investigate the influence of implantation site and recipient sex on the differentiation of hESC-derived PECs in vivo. Male and female mice were implanted with 5x106 hESC-derived PECs either under the kidney capsule, in the gonadal fat pad, or subcutaneously within macroencapsulation (TheraCyteTM) devices. Mice that received PECs within TheraCyteTM devices developed glucosestimulated human C-peptide secretion faster than cells implanted under the kidney capsule or in the gonadal fat pad. Interestingly, hESC-derived PECs implanted under the kidney capsule in females developed glucose-stimulated human C-peptide faster than in males, and secreted higher levels of arginine-stimulated glucagon and GLP-1 than other implantation sites. Furthermore, hESC-derived grafts collected from the kidney capsule and gonadal fat pad sites displayed a mix of endocrine and ductal cells as well as contained cysts whereas TheraCyteTM device grafts displayed mostly endocrine cells and cysts were not observed. Here we demonstrate that the macroencapsulated subcutaneous site and the female recipient can promote faster differentiation of hESC-derived PECs to endocrine cells in mice.

中文翻译：

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不同植入部位和性别对体内人胰腺内胚层细胞向胰岛素分泌细胞分化的影响

很少有研究检查人类胚胎干细胞 (hESC) 衍生的胰腺内胚层细胞 (PEC) 在不同植入部位的分化。在这里，我们研究了植入部位和受体性别对体内 hESC 衍生 PEC 分化的影响。将 5x106 hESC 衍生的 PEC 植入雄性和雌性小鼠的肾囊下、性腺脂肪垫内或皮下大囊化 (TheraCyteTM) 装置内。在 TheraCyteTM 装置中接受 PEC 的小鼠比植入肾囊下或性腺脂肪垫中的细胞更快地产生葡萄糖刺激的人类 C 肽分泌。有趣的是，植入女性肾囊下的 hESC 衍生 PEC 比男性更快地产生葡萄糖刺激的人 C 肽，并分泌比其他植入部位更高水平的精氨酸刺激的胰高血糖素和 GLP-1。此外，从肾囊和性腺脂肪垫部位收集的 hESC 衍生移植物显示内分泌细胞和导管细胞的混合以及包含囊肿，而 TheraCyteTM 装置移植物主要显示内分泌细胞，未观察到囊肿。在这里，我们证明大包皮下部位和雌性受体可以促进 hESC 衍生的 PEC 更快地分化为小鼠的内分泌细胞。