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来自无转基因猪诱导的多能干干细胞的血管内皮细胞用于血管组织工程

Luke Batty¹, Jinkyu Park², Lingfeng Qin³

¹Department of Internal Medicine, Section of Cardiovascular Medicine, Yale Cardiovascular Research Center, Yale School of Medicine, 300 George Street, New Haven, CT 06511, USA; Yale Stem Cell Center, 10 Amistad Street, New Haven, CT 06511, USA; Department of Pathology, Yale University, New Haven, CT 06510, USA.

Acta biomaterialia

|December 16, 2024

概括

研究人员从猪身上开发出无转基因诱导多能干细胞 (iPSC). 这些细胞可以为血管组织工程创建功能性内皮细胞,推进临床前心血管疾病建模.

科学领域:

心血管研究研究心血管研究
干细胞生物学干细胞生物学
组织工程是组织工程.

背景情况:

针对心血管疾病的基于细胞的疗法需要进行广泛的临床前测试.
像猪这样的大型动物模型对于物种对物种的测试至关重要,因为它们与人类有心血管的相似之处.
缺乏合适的猪诱导多能干细胞 (piPSCs) 阻碍了这项研究.

研究的目的:

为了产生与人类iPSC相似的无转基因piPSC.
用于血管应用,将piPSC分化为功能性内皮细胞 (EC).
评估piPSC衍生ECs在组织工程血管导管 (TEVCs) 中的实用性,用于临床前心血管建模.

主要方法:

在优化的介质中使用重编程因子来产生无转基因piPSCs.
使用差异化协议,从piPSC中导出EC.
使用piPSC-ECs来构建TEVCs,然后在小鼠体内作为下静脉腔移植体进行体内测试.

主要成果:

生成无转基因的piPSCs具有真正的多能性.
将piPSC分化为表达相关标记的功能EC.
从piPSC-EC构建了TEVC,这些TEVC显示了流量响应标记的调节.
在体内移植表明了内皮标记体表达,并预防了血栓形成.

结论:

开发的piPSC类似于人类的iPSC,解决了心血管研究中的一个关键瓶.
这些piPSC可以创建功能性的EC和TEVC,用于强大的临床前测试.
这一进步促进了基于细胞的心血管治疗的物种内大型动物建模,使其更接近临床应用.

关键词:

内皮细胞是内皮细胞.猪诱导的多能干细胞干细胞组织工程是组织工程.没有转基因的自由基因.

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