Till truth makes all things plain: human hearts and stem cells.
Till truth makes all things plain: human hearts and stem cells.
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直到真相让一切变得清晰：人类心脏和干细胞。
DOI：
10.1161/circresaha.114.305340
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发表时间：
2014
影响因子：
20.1
通讯作者：
Perin,EmersonC
中科院分区：
文献类型：
--
作者：
Willerson,JamesT;Taylor,Doris;Perin,EmersonC
年轻的供体可用于治疗患有心血管疾病的老年个体。16，17事实上，从健康的年轻供体中获得的同种异体间充质细胞的经内皮素注射在缺血性或非缺血性心肌病患者中似乎是安全的，并且高剂量细胞治疗改善了LV重塑并降低了心力衰竭相关的主要不良心脏事件的发生率。16另一种可用于改善患有多种合并症的老年患者的细胞治疗的方法是使患者的衰老干细胞恢复活力。例如，移植来自诱导过表达心肌素和端粒酶逆转录酶的老年小鼠的间充质基质细胞导致后肢缺血小鼠模型中细胞功能的改善。18同样，用Pim-1激酶离体修饰衰老的人心脏祖细胞已显示出增加细胞增殖和存活。此外，老年小鼠心脏显示出比年轻心脏具有更多的静止c-kit+心脏干细胞，但用干细胞因子刺激这些细胞有效地逆转了年龄相关的心肌病。20研究还表明，使用特定的细胞组合可以提高干细胞治疗的功效。在猪心肌梗死模型中，间充质干细胞和c-kit+干细胞的组合改善了左心室功能，并比单独使用任一种细胞类型显著减少了梗死面积。[21]心肌球衍生细胞在缺血性心肌病患者中的令人鼓舞的结果也表明，使用组合而不是单一类型的干细胞可能更有效。4总之，评估使用选择的成体干细胞治疗缺血性心肌病患者的临床试验产生了令人鼓舞的结果，表明这些疗法是安全的，并可能改善临床结果。基于所了解的情况，我们应该继续努力开发更有效的干细胞疗法。迄今为止进行的研究规模相对较小，随访时间有限，但通过进行更长随访期的大型研究，可能会提高检测到显著治疗效果的可能性，例如III期AAMI试验（骨髓来源的单核细胞[BM-MNC]冠状动脉内回输对急性心肌梗死全因死亡率的影响;临床试验。gov标识符：NCT 01569178），预计将招募3000名患者并随访3年。此外，由于一些患者特异性因素已被证明与干细胞治疗后改善的结果相关，因此在未来的研究中选择更具针对性的研究人群可能是有益的。当代医学科学的负担是开发细胞疗法，该疗法可以最大化身体干细胞的益处，并通过替换内源性干细胞或通过改善其功能或局部生态位的生物活性来增强组织修复。这种研究方法可能会使我们有能力再生整个器官，甚至可能延缓衰老过程。与大多数医学突破一样，成功的干细胞疗法的发展将通过微小的渐进式改进来实现。临床试验是这一过程的重要组成部分，因为最终，干细胞治疗心血管疾病的安全性和有效性的证据只能来自人体研究。每一次临床试验都是一次宝贵的学习经历。从患者特定特征和细胞治疗结果的研究中获得的见解可能会更好地了解...
youthful donors may be used to treat aging individuals with cardiovascular diseases. 16, 17 Indeed, transendocardial injections of allogeneic mesenchymal cells obtained from a healthy young donor seemed to be safe in patients with ischemic or nonischemic cardiomyopathy, and treatment with high cell doses improved LV remodeling and reduced rates of heart failure–associated major adverse cardiac events. 16 Another approach that could be used to improve cell therapy in older patients with multiple comorbidities is to rejuvenate the patient’s senescent stem cells. For example, the transplantation of mesenchymal stromal cells from aged mice that were induced to overexpress myocardin and telomerase reverse transcriptase resulted in improvements in cell function in a mouse model of hindlimb ischemia. 18 Likewise, the ex vivo modification of senescent human cardiac progenitor cells with Pim-1 kinase has been shown to increase cellular proliferation and survival. 19 Furthermore, older mouse hearts were shown to have more quiescent c-kit+ cardiac stem cells than younger hearts, but the stimulation of these cells with stem cell factor effectively reversed age-related cardiomyopathy. 20 Studies have also indicated that the efficacy of stem cell treatments may be enhanced by using specific cell combinations. In a porcine model of myocardial infarction, a combination of mesenchymal and c-kit+ stem cells improved LV function and reduced infarct size significantly more than either cell type did alone. 21 The encouraging results with cardiosphere-derived cells in patients with ischemic cardiomyopathy also suggest that using a combination rather than a single type of stem cell may be more effective. 4 In summary, clinical trials assessing the use of select adult stem cells for treating patients with ischemic cardiomyopathy have produced encouraging results, suggesting that these therapies are safe and could potentially improve clinical outcomes. Based on what has been learned, we should continue our efforts to develop more effective stem cell therapies. The studies performed to date have been relatively small with limited follow-up, but the likelihood of detecting significant treatment effects may be improved by conducting larger studies with longer follow-up periods, such as the phase 3 BAMI trial (The Effect of Intracoronary Reinfusion of Bone Marrow-derived Mononuclear Cells [BM-MNC] on All Cause Mortality in Acute Myocardial Infarction; ClinicalTrials. gov identifier: NCT01569178), which is expected to enroll 3000 patients and follow them for 3 years. Moreover, because some patient-specific factors have been shown to be associated with improved outcomes after stem cell therapy, it may be beneficial to select more targeted study populations in future studies. The burden on contemporary medical science is to develop cell therapies that can maximize the benefits of the body’s stem cells and enhance tissue repair by replacing endogenous stem cells or by improving their function or the bioactivity of the local niche. This investigative approach may lead to our ability to regenerate whole organs and possibly even delay the aging process. As with most medical breakthroughs, the development of successful stem cell therapies will be achieved through small, incremental improvements. Clinical trials are a vital part of this process because, ultimately, proof of the safety and efficacy of stem cell therapy for cardiovascular disease can come only from human studies. Each clinical trial can be a valuable learning experience. Insight gained from studies of patient-specific characteristics and cell therapy outcomes may lead to a better understanding of the …