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心内细胞移植的比较:自体骨骼肌成肌细胞与骨髓细胞

Comparison of intracardiac cell transplantation: autologous skeletal myoblasts versus bone marrow cells.

作者信息

Zenovich A G, Davis B H, Taylor D A

机构信息

Center for Cardiovascular Repair, 312 Church Street SE, NHH 7-105A, Minneapolis, MN 55455, USA.

出版信息

Handb Exp Pharmacol. 2007(180):117-65. doi: 10.1007/978-3-540-68976-8_6.

Abstract

An increasing number of patients living with cardiovascular disease (CVD) and still unacceptably high mortality created an urgent need to effectively treat and prevent disease-related events. Within the past 5 years, skeletal myoblasts (SKMBs) and bone marrow (or blood)-derived mononuclear cells (BMNCs) have demonstrated preclinical efficacy in reducing ischemia and salvaging already injured myocardium, and in preventing left ventricular (LV) remodeling, respectively. These findings have been translated into clinical trials, so far totaling over 200 patients for SKMBs and over 800 patients for BMNCs. These safety/feasibility and early phase II studies showed promising but somewhat conflicting symptomatic and functional improvements, and some safety concerns have arisen. However, the patient population, cell type, dose, time and mode of delivery, and outcome measures differed, making comparisons problematic. In addition, the mechanisms through which cells engraft and deliver their beneficial effects remain to be fully elucidated. It is now time to critically evaluate progress made and challenges encountered in order to select not only the most suitable cells for cardiac repair but also to define appropriate patient populations and outcome measures. Reiterations between bench and bedside will increase the likelihood of cell therapy success, reduce the time to development of combined of drug- and cell-based disease management algorithms, and offer these therapies to patients to achieve a greater reduction of symptoms and allow for a sustained improvement of quality of life.

摘要

心血管疾病(CVD)患者数量不断增加,且死亡率仍高得令人无法接受,这迫切需要有效治疗和预防与疾病相关的事件。在过去5年中,骨骼肌成肌细胞(SKMBs)和骨髓(或血液)来源的单核细胞(BMNCs)已分别在减少缺血、挽救已受损心肌以及预防左心室(LV)重构方面显示出临床前疗效。这些发现已转化为临床试验,到目前为止,SKMBs的临床试验患者总数超过200例,BMNCs的超过800例。这些安全性/可行性和早期II期研究显示出有希望但在症状和功能改善方面存在一定冲突的结果,并且出现了一些安全问题。然而,患者群体、细胞类型、剂量、递送时间和方式以及结果测量方法各不相同,使得比较存在问题。此外,细胞植入并发挥其有益作用的机制仍有待充分阐明。现在是时候批判性地评估已取得的进展和遇到的挑战了,以便不仅选择最适合心脏修复的细胞,而且确定合适的患者群体和结果测量方法。基础研究和临床实践之间的反复迭代将增加细胞治疗成功的可能性,减少基于药物和细胞的疾病管理算法的开发时间,并将这些疗法提供给患者,以更大程度地减轻症状并持续改善生活质量。

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