After a myocardial infarction, heart tissue becomes irreversibly damaged, leading to scar formation and inevitably ischemic heart failure. Of the many available interventions after a myocardial infarction, such as percutaneous intervention or pharmacological optimization, none can reverse the ischemic insult on the heart and restore cardiac function. Thus, the only available cure for patients with scarred myocardium is allogeneic heart transplantation, which comes with extensive costs, risks, and complications. However, multiple studies have shown that the heart is, in fact, not an end-stage organ and that there are endogenous mechanisms in place that have the potential to spark regeneration. Stem cell therapy has emerged as a potential tool to tap into and activate this endogenous framework. Particularly promising are stem cells derived from cardiac tissue itself, referred to as cardiosphere-derived cells (CDCs). CDCs can be extracted and isolated from the patient's myocardium and then administered by intramyocardial injection or intracoronary infusion. After early success in the animal model, multiple clinical trials have demonstrated the safety and efficacy of autologous CDC therapy in humans. Clinical trials with allogeneic CDCs showed early promising results and pose a potential "off-the-shelf" therapy for patients in the acute setting after a myocardial infarction. The mechanism responsible for CDC-induced cardiac regeneration seems to be a combination of triggering native cardiomyocyte proliferation and recruitment of endogenous progenitor cells, which most prominently occurs via paracrine effects. A further understanding of the mediators involved in paracrine signaling can help with the development of a stem cell-free therapy, with all the benefits and none of the associated complications.

中文翻译：

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心球来源的细胞与缺血性心力衰竭。

心肌梗塞后，心脏组织不可逆转地受损，导致疤痕形成和不可避免的缺血性心力衰竭。在心肌梗塞后的许多可用干预措施（例如经皮干预或药理优化）中，没有一种能够逆转对心脏的缺血性损伤并恢复心脏功能。因此，对于有疤痕心肌的患者，唯一可用的治疗方法是同种异体心脏移植，这会带来巨大的成本，风险和并发症。但是，多项研究表明，心脏实际上不是末期器官，并且存在一些内在机制，可能激发火花。干细胞疗法已成为一种进入并激活这种内源性框架的潜在工具。特别有希望的是源自心脏组织本身的干细胞，称为心球来源的细胞（CDC）。可以从患者的心肌中提取和分离CDC，然后通过心肌内注射或冠状动脉内输注进行给药。在动物模型中取得早期成功之后，多项临床试验证明了自体CDC治疗对人类的安全性和有效性。异基因CDC的临床试验显示了早期有希望的结果，并为心肌梗死后的急性患者提供了一种潜在的“现成”疗法。造成CDC诱导的心脏再生的机制似乎是触发天然心肌细胞增殖和内源祖细胞募集的组合，这最主要是通过旁分泌作用发生的。