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通过适应性内皮细胞对人类小岛的血管化,以实现持久且功能性的皮下移植

Ge Li^1,2, Rebecca Craig-Schapiro^1,3, David Redmond¹

¹Division of Regenerative Medicine, Hartman Institute for Therapeutic Organ Regeneration, Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.

Science advances

|January 29, 2025

概括

重编程血管内皮细胞 (R-VECs) 在体外和体内成功地血管化了人体岛屿. 这种方法支持岛屿功能,并逆转糖尿病小鼠的高血糖,为岛屿移植提供了一个有希望的策略.

科学领域:

内分泌学在内分泌学.
血管生物学血管生物学
再生医学是一种再生医学.

背景情况:

内皮细胞 (ECs) 对于胰腺小岛恒温至关重要.
血管化对于体外小岛功能和移植至关重要,但仍然是一个重大挑战.

研究的目的:

研究人类重编程血管ECs (R-VECs) 对人类小岛的功能血管化的潜力.
在糖尿病小鼠模型中评估R-VEC血管化的小岛的治疗疗效.

主要方法:

在体外功能评估与R-VEC共同培养的人类小岛,包括葡萄糖刺激的胰岛素分泌和流入.
在糖尿病小鼠体内进行R-VEC血管化人类小岛的皮下移植.
单细胞RNA测序以分析小岛微环境中的R-VEC适应.

主要成果:

在实验室中,R-VECs使人体小岛的功能血管化成为可能,保持了葡萄糖刺激的胰岛素分泌.
移植R-VEC血管化的小岛在糖尿病小鼠中逆转高血糖,维持人体胰岛素水平.
植入的R-VECs与宿主血管系进行了解剖,并在体内获得了小岛EC特有的特征.

结论:

人类R-VECs可以建立一个功能性血管,在体外和体内都支持小岛恒温.
通过R-VEC介导的血管化是改善小岛移植结果的有希望的策略.
这种方法有可能用于治疗1型糖尿病和其他需要功能性小岛移植的疾病.

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