Cardiac Regenerative Therapy Using Gene-Edited Stem Cells to Improve Transplantation Outcomes

使用基因编辑干细胞改善移植结果的心脏再生疗法

基本信息

  • 批准号:
    10905166
  • 负责人:
  • 金额:
    $ 40.04万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-09-01 至 2024-08-31
  • 项目状态:
    已结题

项目摘要

Cardiovascular disease is the leading cause of morbidity and mortality in the United States. A significant loss of cardiomyocytes from myocardial infarction (MI) can result in progressive deterioration of cardiac function. Many patients do not recover their cardiac function despite optimal medical therapies and develop progressive adverse structural and electrical remodeling leading to heart failure (HF) with lethal consequences. HF remains a deadly clinical syndrome with 5-year mortality of 45–60%. Therefore, there is a compelling need to seek new options for patients in end-stage HF. Since adult cardiac myocytes are unable to proliferate sufficiently to replace the damaged tissue, stem cell therapy represents a new promising approach for the treatment of end-stage HF, since it aims at generating new functional myocardium and inducing neoangiogenesis. However, one of the main challenges of cardiac stem cell transplantation is the survival and retention of transplanted cells in the hostile milieu. We have recently published compelling data to demonstrate the one of the main causes of transplanted stem cell loss is inflammation in a murine post-MI model. Therefore, the overarching goal of this proposal is to target genes involved in the inflammatory pathway in somatic cells that will be transplanted, to improve transplantation outcomes in end-stage HF. The proposal addresses the critical role of inflammation induced-cell death that severely impede cardiac stem cell therapy. Successful completion will pave way to facilitate future personalized cardiovascular care for patients with end-stage HF and the translation of transplantation therapies from bench side to clinical practice.
心血管疾病是美国发病率和死亡率的主要原因。的显著损失 心肌梗死(MI)引起的心肌细胞损伤可导致心脏功能的进行性恶化。 尽管有最佳的药物治疗,许多患者的心脏功能仍无法恢复, 不良的结构和电重塑导致心力衰竭(HF),造成致命后果。HF残留 一种致命的临床综合征,5年死亡率为45- 60%。因此,迫切需要寻求新的 终末期HF患者的选择。由于成年心肌细胞不能充分增殖, 损伤组织,干细胞疗法代表了治疗终末期HF的新的有希望的方法, 因为其目的是产生新的功能性心肌和诱导新血管生成。然而,主要的 心脏干细胞移植的挑战是移植细胞在敌对环境中的存活和保留。 环境。我们最近发表了令人信服的数据,以证明移植的主要原因之一, 干细胞损失是鼠MI后模型中的炎症。因此,本提案的总体目标是 靶基因参与炎症途径的体细胞,将被移植,以改善 终末期HF的移植结局。该提案提出了炎症诱导细胞的关键作用, 严重阻碍心脏干细胞治疗的死亡。成功完成将为促进未来 终末期心力衰竭患者的个性化心血管护理和移植疗法的转化 从实验室到临床实践。

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