Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry, and Biomedical Science, Queen's University Belfast, Belfast, UK.
Université de Paris, Innovative Therapies in Haemostasis, INSERM, Paris, France.
Stem Cells Transl Med. 2021 Nov;10 Suppl 2(Suppl 2):S54-S61. doi: 10.1002/sctm.21-0022.
Ischemic vascular disease is a major cause of mortality and morbidity worldwide, and regeneration of blood vessels in perfusion-deficient tissues is a worthwhile therapeutic goal. The idea of delivering endothelial stem/progenitor cells to repair damaged vasculature, reperfuse hypoxic tissue, prevent cell death, and consequently diminish tissue inflammation and fibrosis has a strong scientific basis and clinical value. Various labs have proposed endothelial stem/progenitor cell candidates. This has created confusion, as there are profound differences between these cell definitions based on isolation methodology, characterization, and reparative biology. Here, a stricter definition based on stem cell biology principles is proposed. Although preclinical studies have often been promising, results from clinical trials have been highly contradictory and served to highlight multiple challenges associated with disappointing therapeutic benefit. This article reviews recent accomplishments in the field and discusses current difficulties when developing endothelial stem cell therapies. Emerging evidence that disputes the classic view of the bone marrow as the source for these cells and supports the vascular wall as the niche for these tissue-resident endothelial stem cells is considered. In addition, novel markers to identify endothelial stem cells, including CD157, EPCR, and CD31 VEGFR2 IL33 Sox9 , are described.
缺血性血管疾病是全球范围内导致死亡和发病的主要原因，而在灌注不足的组织中再生血管是一个有价值的治疗目标。将内皮干细胞/祖细胞输送到受损的血管中以修复受损的血管、重新灌注缺氧组织、防止细胞死亡，从而减少组织炎症和纤维化的想法具有坚实的科学基础和临床价值。不同的实验室已经提出了内皮干细胞/祖细胞的候选物。这造成了混淆，因为基于分离方法、特征和修复生物学的这些细胞定义之间存在着深刻的差异。在这里，根据干细胞生物学原理提出了一个更严格的定义。尽管临床前研究通常很有希望，但临床试验的结果却存在很大的矛盾，突出了与令人失望的治疗效果相关的多个挑战。本文综述了该领域的最新进展，并讨论了开发内皮干细胞疗法的当前困难。新兴的证据对骨髓作为这些细胞来源的经典观点提出了质疑，并支持血管壁作为这些组织驻留的内皮干细胞的龛位。此外，还描述了用于鉴定内皮干细胞的新型标记物，包括 CD157、EPCR 和 CD31、VEGFR2、IL33、Sox9 等。
