Department of Bioengineering, Northeastern University, Boston, MA, USA.
Department of Bioengineering, Northeastern University, Boston, MA, USA.
Cell Rep Methods. 2024 Mar 25;4(3):100732. doi: 10.1016/j.crmeth.2024.100732. Epub 2024 Mar 18.
An autologous source of vascular endothelial cells (ECs) is valuable for vascular regeneration and tissue engineering without the concern of immune rejection. The transcription factor ETS variant 2 (ETV2) has been shown to directly convert patient fibroblasts into vascular EC-like cells. However, reprogramming efficiency is low and there are limitations in EC functions, such as eNOS expression. In this study, we directly reprogram adult human dermal fibroblasts into reprogrammed ECs (rECs) by overexpressing SOX17 in conjunction with ETV2. We find several advantages to rEC generation using this approach, including improved reprogramming efficiency, increased enrichment of EC genes, formation of large blood vessels carrying blood from the host, and, most importantly, expression of eNOS in vivo. From these results, we present an improved method to reprogram adult fibroblasts into functional ECs and posit ideas for the future that could potentially further improve the reprogramming process.
自体血管内皮细胞（ECs）来源对于血管再生和组织工程具有重要价值，不会引起免疫排斥反应。转录因子 ETS 变体 2（ETV2）已被证明可直接将患者成纤维细胞转化为血管 EC 样细胞。然而，重编程效率低，EC 功能存在局限性，例如 eNOS 表达。在这项研究中，我们通过过表达 SOX17 与 ETV2 直接将成人皮肤成纤维细胞重编程为重编程的 EC（rEC）。我们发现，使用这种方法生成 rEC 具有几个优点，包括提高了重编程效率，增加了 EC 基因的富集，形成了携带宿主血液的大血管，并且最重要的是，在体内表达了 eNOS。根据这些结果，我们提出了一种将成纤维细胞重编程为功能性 EC 的改进方法，并提出了一些未来的想法，这些想法有可能进一步改进重编程过程。
