Stem-cell cardiospheres for myocardial regeneration: advancing cell therapy in myocardial infarction and heart failure
Stem-cell cardiospheres for myocardial regeneration: advancing cell therapy in myocardial infarction and heart failure
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用于心肌再生的干细胞心脏球：推进心肌梗塞和心力衰竭的细胞治疗
DOI：
10.1113/jp276660
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Lee S
中科院分区：
文献类型：
--
作者：
Lee S
每五个40岁以上的男性中就有一个在一生中的某个时候有心脏病发作的风险。心肌梗死（MI），也称为心脏病发作，是一种临床综合征，其中心肌血流的剥夺导致心肌细胞死亡和心脏功能恶化，导致缺血性心肌病和最终的心力衰竭（HF）。因此，HF仍然是全球上升最快的心脏病，是北美最常见的死亡原因。对MI和HF的有效治疗的研究已经导致了对干细胞（包括人胚胎干细胞、诱导的多能干细胞、心脏祖细胞和骨髓来源的干细胞）用于心脏修复和再生的用途的研究。然而，目前的干细胞疗法已经证明了受损心肌的适度重建和异质性临床结果。心脏再生是自然界中的默认状态，但其能力在成年人中大大减弱，这给开发有效的细胞疗法带来了巨大挑战。尽管如此，心脏微球（CSps）最近已成为梗死心脏修复和再生的一个有前途的途径。CSp是心脏干细胞衍生的微组织（70-150 μm），由核心中的未分化干细胞和包装成专门三维结构的心脏定向细胞外层组成。这种复杂的三维模型保护干细胞免受细胞氧化应激的影响，从而增加干细胞的干细胞性、旁分泌能力和治疗潜力。然而，通过常规方法将CSp直接植入受损的心肌中，由于其三维结构而增加了发生栓塞的可能性。因此，需要进一步研究以确定CSp植入的合适递送途径，以最大限度地发挥其治疗潜力。
One out of every five men over the age of 40 are at risk of developing a heart attack at some point during their lifetime. Myocardial infarction (MI), also known as heart attack, is a clinical syndrome in which deprivation of blood flow to the heart muscle causes cardiomyocyte death and deterioration of heart function, resulting in ischaemic cardiomyopathy and eventual heart failure (HF). For this reason, HF remains the most rapidly rising heart disease globally and represents the most common cause of death in North America. The search for effective treatments of MI and HF has led to investigations into the use of stem cells including human embryonic stem cells, induced-pluripotent stem cells, cardiac progenitor cells and bone marrow-derived stem cells for heart repair and regeneration. However, current stem cell therapies have demonstrated a modest reconstitution in damaged myocardium and heterogeneous clinical outcomes. Heart regeneration is the default state in nature but its capacity is greatly diminished in human adults, creating a big challenge in developing effective cell therapy treatments. Nonetheless, cardiospheres (CSps) have recently emerged as a promising avenue for cardiac repair and regeneration in infarcted hearts. CSps are cardiac explant-derived microtissues (70–150 μm) that consist of undifferentiated stem cells in the core and an outer layer of cardiac-committed cells packaged into a specialized three-dimensional structure. This complex three-dimensional model protects the stem cells from cellular oxidative stress, resulting in their increased stemness, paracrine potency and therapeutic potential. However, implantation of CSps via conventional methods directly into damaged heart muscle raises the possibility of developing an embolism due to its three-dimensional structure. Therefore, further research is warranted to determine a suitable delivery route for CSp implantation to maximize its therapeutic potential.