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

新生儿干细胞分泌组作为心力衰竭的新型再生疗法

• 批准号: 538821-2019
• 负责人: Maynes, Jason
• 金额: $ 7.76万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Collaborative Health Research Projects
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=692916
• 关键词: Neonatal; Stem; Cell; Secretomes; Novel

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.

心力衰竭的预后普遍较差，只有50%的患者在诊断后能再存活5年。治疗心力衰竭的药物对患者生存率的影响很小，主要是针对疾病症状的控制。再生医学，即促进心脏自我修复，是一种新的，潜在的破坏性的治疗范式，可以为器官功能提供持久的改变。在确定如何利用这一概念获益时，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。使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中分离出的具有再生潜力的细胞（干细胞）分泌的分子与从老年患者中分离出的细胞不同。我们现在建议利用这种能力来开发一种新的心力衰竭患者的生物治疗方法。我们已经收集了一组来自儿科心脏手术患者的初始样本并进行了初步表征。在这个项目中，我们将扩展我们的分析，包括更广泛的患者年龄和心脏诊断。将在已建立的测定中测试分泌的混合物的再生潜力，并确定其组成，从而阐明具有最高治疗潜力的组分。使用我们合作小组的一名成员发明的新型生物相容性支架，我们将创造一种最佳的递送载体，用于注射到患者衰竭的心脏中，允许持续释放修复分子。最后，我们将在大型心力衰竭动物模型中测试新疗法的实用性。我们将与我们的行业合作伙伴Bluerock Therapeutics密切合作，该公司的唯一任务是将再生疗法推向市场，以便立即进行商业应用并转化为患者护理。