Li Ge, Craig-Schapiro Rebecca, Redmond David, Chen Kevin, Lin Yang, Geng Fuqiang, Gao Meng, Rabbany Sina Y, Suresh Gayathri, Pearson Bradley, Schreiner Ryan, Rafii Shahin
Division of Regenerative Medicine, Hartman Institute for Therapeutic Organ Regeneration, Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
Biological Sciences Department, Bronx Community College, City University of New York, New York, NY, USA.
Sci Adv. 2025 Jan 31;11(5):eadq5302. doi: 10.1126/sciadv.adq5302. Epub 2025 Jan 29.
Tissue-specific endothelial cells (ECs) are critical for the homeostasis of pancreatic islets and most other tissues. In vitro recapitulation of islet biology and therapeutic islet transplantation both require adequate vascularization, which remains a challenge. Using human reprogrammed vascular ECs (R-VECs), human islets were functionally vascularized in vitro, demonstrating responsive, dynamic glucose-stimulated insulin secretion and Ca influx. Subcutaneous transplantation of islets with R-VECs reversed hyperglycemia in diabetic mice, with high levels of human insulin detected within recipient serum and relapses of hyperglycemia following graft removal. Examination of retrieved grafts demonstrated that engrafted human islets were mainly vascularized by the cotransplanted R-VECs, which had anastomosed with the host microcirculation. Notably, single-cell RNA-sequencing revealed that R-VECs, when cocultured with islets, acquired islet EC-specific characteristics. Together, R-VECs establish an adaptable vascular niche that supports islet homeostasis both in vitro and in vivo.
组织特异性内皮细胞（ECs）对于胰岛和大多数其他组织的稳态至关重要。胰岛生物学的体外重现和治疗性胰岛移植都需要充足的血管化，而这仍然是一个挑战。使用人重编程血管内皮细胞（R-VECs），人胰岛在体外实现了功能性血管化，表现出响应性、动态葡萄糖刺激的胰岛素分泌和钙离子内流。将胰岛与R-VECs进行皮下移植可逆转糖尿病小鼠的高血糖，在受体血清中检测到高水平的人胰岛素，并且在移植物移除后高血糖复发。对取回的移植物进行检查表明，植入的人胰岛主要由共移植的R-VECs血管化，这些R-VECs已与宿主微循环吻合。值得注意的是，单细胞RNA测序显示，R-VECs与胰岛共培养时获得了胰岛EC特异性特征。总之，R-VECs建立了一个适应性血管微环境，在体外和体内均支持胰岛稳态。
