Terzic Andre, Behfar Atta
Center for Regenerative Medicine, Mayo Clinic, Rochester, MN; Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN.
Center for Regenerative Medicine, Mayo Clinic, Rochester, MN; Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN; Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN.
Trends Cardiovasc Med. 2016 Jul;26(5):395-404. doi: 10.1016/j.tcm.2016.01.003. Epub 2016 Jan 28.
Patient-derived stem cells enable promising regenerative strategies, but display heterogenous cardiac reparative proficiency, leading to unpredictable therapeutic outcomes impeding practice adoption. Means to establish and certify the regenerative potency of emerging biotherapies are thus warranted. In this era of clinomics, deconvolution of variant cytoreparative performance in clinical trials offers an unprecedented opportunity to map pathways that segregate regenerative from non-regenerative states informing the evolution of cardio-regenerative quality systems. A maiden example of this approach is cardiopoiesis-mediated lineage specification developed to ensure regenerative performance. Successfully tested in pre-clinical and early clinical studies, the safety and efficacy of the cardiopoietic stem cell phenotype is undergoing validation in pivotal trials for chronic ischemic cardiomyopathy offering the prospect of a next-generation regenerative solution for heart failure.
患者来源的干细胞为有前景的再生策略提供了可能,但表现出异质性的心脏修复能力,导致不可预测的治疗结果,阻碍了该疗法的实际应用。因此,有必要建立并认证新兴生物疗法的再生潜力。在这个临床组学时代,对临床试验中细胞修复性能变异的反卷积分析提供了一个前所未有的机会,来绘制区分再生状态和非再生状态的途径,为心脏再生质量体系的发展提供信息。这种方法的首个实例是为确保再生性能而开发的心脏生成介导的谱系定向。在临床前和早期临床研究中成功测试后,心脏生成干细胞表型的安全性和有效性正在针对慢性缺血性心肌病的关键试验中进行验证,为心力衰竭提供了下一代再生解决方案的前景。