Data_Sheet_1_Recent Advances in Endothelial Progenitor Cells Toward Their Use in Clinical Translation.pdf

Since the discovery of Endothelial Progenitor Cells (EPC) by Asahara and colleagues in 1997, an increasing number of preclinical studies have shown that EPC based therapy is feasible, safe, and efficacious in multiple disease states. Subsequently, this has led to several, mainly early phase, clinical trials demonstrating the feasibility and safety profile of EPC therapy, with the suggestion of efficacy in several conditions including ischemic heart disease, pulmonary arterial hypertension and decompensated liver cirrhosis. Despite the use of the common term “EPC,” the characteristics, manufacturing methods and subset of the cell type used in these studies often vary significantly, rendering clinical translation challenging. It has recently been acknowledged that the true EPC is the endothelial colony forming cells (ECFC). The objective of this review was to summarize and critically appraise the registered and published clinical studies using the term “EPC,” which encompasses a heterogeneous cell population, as a therapeutic agent. Furthermore, the preclinical data using ECFC from the PubMed and Web of Science databases were searched and analyzed. We noted that despite the promising effect of ECFC on vascular regeneration, no clinical study has stemmed from these preclinical studies. We showed that there is a lack of information registered on www.clinicaltrials.gov for EPC clinical trials, specifically on cell culture methods. We also highlighted the importance of a detailed definition of the cell type used in EPC clinical trials to facilitate comparisons between trials and better understanding of the potential clinical benefit of EPC based therapy. We concluded our review by discussing the potential and limitations of EPC based therapy in clinical settings.

自1997年Asahara及其同事发现内皮祖细胞（Endothelial Progenitor Cells，EPC）以来，越来越多的临床前研究证实，基于EPC的治疗方法在多种疾病状态下具有可行性、安全性和有效性。随后，这一发现促使多项主要处于早期阶段的临床试验得以开展，证实了EPC疗法的可行性和安全性特征，并在缺血性心脏病、肺动脉高压和失代偿期肝硬化等数种疾病条件中显示出疗效的潜力。尽管“EPC”这一通用术语被广泛使用，但研究中使用的细胞类型、制备方法和特征往往存在显著差异，这使得临床转化变得极具挑战性。近期，人们普遍认识到，真正的EPC是内皮集落形成细胞（Endothelial Colony Forming Cells，ECFC）。本综述旨在总结和批判性地评估使用“EPC”这一术语所进行的注册和已发表的临床研究，该术语涵盖了异质细胞群体，并将其作为治疗剂。此外，我们还检索并分析了PubMed和Web of Science数据库中关于ECFC的前临床数据。我们注意到，尽管ECFC在血管再生方面显示出有前景的效果，但尚未有临床研究由此类前临床研究产生。我们指出，在www.clinicaltrials.gov上注册的EPC临床试验信息缺乏，特别是关于细胞培养方法的信息。我们还强调了在EPC临床试验中详细定义所使用细胞类型的重要性，以促进试验间的比较，并更好地理解基于EPC疗法的潜在临床益处。最后，我们在综述中讨论了EPC疗法在临床环境中的潜力和局限性。