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Endothelial reprogramming for vascular regeneration: Past milestones and future directions
Seminars in Cell & Developmental Biology ( IF 6.2 ) Pub Date : 2021-09-20 , DOI: 10.1016/j.semcdb.2021.09.003
Matthew Wingo 1 , Shahin Rafii 1
Affiliation  

Endothelial cells are critical mediators of health and disease. Regenerative medicine techniques that target the endothelium hold vast promise for improving lifespan and quality of life worldwide. Regenerative therapies via induced pluripotent stem cells (IPSCs) have helped demonstrate disease mechanisms, but so far, concerns regarding their function, malignant potential, and expense have limited therapeutic potential. One alternative approach is direct reprogramming of somatic cells, which avoids the pluripotent state and allows for in vivo reprogramming. Transcription factors from endothelial development have yielded essential transcription factors and small molecules that induce endothelial cell fate. Most direct cell reprogramming strategies targeting endothelial cells use ETV2, a pioneer transcription factor to specify endothelial lineage via histone-modifying enzymes. Many different types of starting cells and strategies, including lentiviral transduction, inducing innate immunity, and small molecule signaling have been leveraged for reprogramming. However, so far therapeutic benefit of these strategies remains unproven. Future research will have to solve scalability, safety, and efficacy hurdles before being ready for the clinic. However, researchers have already discovered meaningful insights into disease mechanisms and development through direct reprogramming.



中文翻译:

血管再生的内皮重编程:过去的里程碑和未来的方向

内皮细胞是健康和疾病的关键介质。针对内皮的再生医学技术对提高全世界的寿命和生活质量具有广阔的前景。通过诱导多能干细胞 (IPSC) 进行的再生疗法有助于证明疾病机制,但到目前为止,对其功能、恶性潜能和费用的担忧限制了治疗潜力。一种替代方法是体细胞的直接重编程,它避免了多能状态并允许体内重编程。来自内皮发育的转录因子已经产生了诱导内皮细胞命运的基本转录因子和小分子。大多数针对内皮细胞的直接细胞重编程策略使用 ETV2,通过组蛋白修饰酶指定内皮谱系的先驱转录因子。许多不同类型的起始细胞和策略,包括慢病毒转导、诱导先天免疫和小分子信号传导,已被用于重编程。然而,到目前为止,这些策略的治疗益处仍未得到证实。未来的研究必须在为临床做好准备之前解决可扩展性、安全性和有效性方面的障碍。然而,研究人员已经通过直接重编程发现了对疾病机制和发展的有意义的见解。到目前为止,这些策略的治疗益处仍未得到证实。未来的研究必须在为临床做好准备之前解决可扩展性、安全性和有效性方面的障碍。然而,研究人员已经通过直接重编程发现了对疾病机制和发展的有意义的见解。到目前为止,这些策略的治疗益处仍未得到证实。未来的研究必须在为临床做好准备之前解决可扩展性、安全性和有效性方面的障碍。然而,研究人员已经通过直接重编程发现了对疾病机制和发展的有意义的见解。

更新日期:2021-09-20
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