Clinical Studies of Cell Therapy in Cardiovascular Medicine: Recent Developments and Future Directions.
Clinical Studies of Cell Therapy in Cardiovascular Medicine: Recent Developments and Future Directions.
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DOI：
10.1161/circresaha.118.311217
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发表时间：
2018-07-06
影响因子：
20.1
通讯作者：
Hare JM
中科院分区：
文献类型：
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作者：
Banerjee MN;Bolli R;Hare JM
鉴于全球心血管疾病的患病率不断上升，严重心力衰竭的治疗选择有限，迫切需要利用心脏再生能力的新技术。干细胞的治疗用途具有逆转心肌损伤和改善心脏功能的潜力，与目前大多数仅缓解心力衰竭症状的医学疗法相反。近20年来，200多项心血管疾病试验表明，大多数细胞类型是安全的;然而，它们的疗效仍然存在争议，限制了这种疗法从研究到实践的过渡。从这些初步研究中吸取的经验教训正在推动新的临床试验的设计;更高保真的细胞分离技术，标准化的条件，更一致地使用最先进的测量技术，以及评估多个终点，以获得对干细胞功效的见解。临床试验的转化几乎超过了我们对机制的理解，个体患者因素可能在干细胞疗效中发挥重要作用。因此，仔细分析剂量，输送方法和理想的患者群体是将细胞治疗从研究转化为实践所必需的。我们正处于该领域的关键阶段，许多相对较小的临床试验的信息必须指导仔细执行的疗效试验。更大规模的疗效试验正在启动，以回答有关旧的第一代干细胞疗法的问题，而新的第二代产品正在被引入临床领域。本文回顾了心血管疾病细胞疗法临床研究的现状，重点介绍了该领域的争议、临床试验设计的改进以及令人兴奋的新细胞产品的应用。
Given the rising prevalence of cardiovascular disease worldwide and the limited therapeutic options for severe heart failure, novel technologies that harness the regenerative capacity of the heart are sorely needed. The therapeutic use of stem cells has the potential to reverse myocardial injury and improve cardiac function, in contrast to most current medical therapies that only mitigate heart failure symptoms. Nearly two decades and more than 200 trials for cardiovascular disease have revealed that most cell types are safe; however, their efficacy remains controversial, limiting the transition of this therapy from investigation to practice. Lessons learned from these initial studies are driving the design of new clinical trials; higher fidelity of cell isolation techniques, standardization of conditions, more consistent use of state of the art measurement techniques, and assessment of multiple endpoints in order to garner insights into the efficacy of stem cells. Translation to clinical trials has almost outpaced our mechanistic understanding, and individual patient factors likely play a large role in stem cell efficacy. Therefore, careful analysis of dosing, delivery methods and the ideal patient populations is necessary to translate cell therapy from research to practice. We are at a pivotal stage in the field in which information from many relatively small clinical trials must guide carefully executed efficacy trials. Larger efficacy trials are being launched to answer questions about older, first-generation stem cell therapeutics, while novel, second-generation products are being introduced into the clinical realm. This review critically examines the current state of clinical research on cell-based therapies for cardiovascular disease, highlighting the controversies in the field, improvements in clinical trial design and the application of exciting new cell products.