Neonatal Stem Cell Secretomes as a Novel Regenerative Therapy for Heart Failure

心力衰竭的预后普遍较差，只有50%的患者在确诊后能再存活5年。现有的治疗心力衰竭的药物对患者的生存影响不大，主要是针对疾病症状的控制。促进心脏自我修复的再生医学是一种新的、具有潜在破坏性的治疗模式，可以为器官功能提供持久的改变。为了确定如何利用这一概念，我们和其他人描述了非常年轻的患者（新生儿）的心脏如何具有更高的内在修复和再生能力。利用接受心脏直视手术的儿科患者的组织样本，我们发现从新生儿心脏分离的具有再生潜力的细胞（干细胞）分泌的分子不同于从老年患者分离的细胞。我们现在建议利用这种能力为心力衰竭患者提供一种新的生物疗法。我们收集并初步鉴定了一组来自小儿心脏手术患者的初始样本。在这个项目中，我们将扩大我们的分析，包括更广泛的患者年龄和心脏诊断。将在所建立的分析中测试分泌混合物的再生潜力，并确定其组成，阐明具有最高治疗潜力的成分。利用我们合作小组的一名成员发明的一种新型生物相容性支架，我们将创造一种最佳的运载工具，用于注射到衰竭患者的心脏中，允许修复分子的持续释放。最后，我们将在心力衰竭的大型动物模型中测试新疗法的效用。我们将与我们的行业合作伙伴Bluerock Therapeutics密切合作，后者的唯一任务是将再生疗法推向市场，允许立即进行商业应用并转化为患者护理。

Heart failure has a universally poor outcome, with only 50% of patients surviving a further five years after diagnosis. The medications that are available for heart failure have little impact onpatient survival, mostly targeting the control of disease symptoms. Regenerative medicine, where the heart is promoted to repair itself, is a new, potentially disruptive, treatmentparadigm that could provide lasting change to organ function. In determining how this concept could be harnessed for benefit, we and others have described how the hearts of very young patients (neonates) have a higher intrinsic ability to repair and regenerative themselves. Using tissue samples from pediatric patients undergoing open heart surgery, we have foundthat cells with regenerative potential (stem cells) isolated from neonatal hearts secrete different molecules than cells isolated from older patients. We now propose to harness this capacity into a novel biologic therapy for heart failure patients.We have collected and preliminarily characterized an initial set of samples from pediatric heart surgery patients. In this project, we will expand our analysis to include a broader range of patient age and cardiac diagnosis. The secreted mixtures will be tested for regenerative potential in established assays, and their composition determined, illuminating the components with the highest therapeutic potential. Using a novel biocompatible scaffold invented by a member of our collaborative group, we will create an optimal delivery vehicle for injection into the failing hearts of patients, allowing for sustained release of the reparative molecules. Finally, we will test the utility of the new therapies in a large animal model of heart failure. We will work in close collaboration with our industry partner, Bluerock Therapeutics, whose sole mandate is to bring regenerative therapies to market, allowing for immediate commercial application and translation into patient care.