Injectable Biomaterial for Treating Hypoplastic Left Heart Syndrome

在过去的30年里，在提高CHD儿童存活率方面取得了很大进展，但 这种曾经致命的疾病现在是一种可控的长期疾病。在这些人中，有 左心发育不全综合征面临最糟糕的结局，因为他们只剩下一个心室 (右心室)，最终衰竭。这些孩子要么长期患病 比如运动耐力差，执行功能下降，社交技能差。在 最糟糕的是，他们被列入移植名单，在最需要短期生存的队列中 是50%，移植物在需要新心脏之前的最长寿命大约是12年。 这项研究的目标是为两个阶段1的联合治疗提供FDA支持的数据 FDA批准的治疗方法；心脏祖细胞和去细胞猪心 细胞外基质。细胞疗法在儿童中很有希望，但与成人研究细胞相似 不会坚持太久，会被移植到有病的微环境中。在三个不同的目标中， 我们将检查这种联合疗法在免疫功能低下和 免疫能力强的大鼠，随后是大型动物猪的研究。这些数据不仅将提供 FDA IND的关键数据，但也将阐明潜在的生理机制 这些疗法所起的作用。 先天性心脏病发生在所有新生儿中的近1%，占大多数 对于常见的出生缺陷，这项研究的潜在影响不能被低估。信息 从这项研究中收集到的信息不仅将改善每年近40,000名儿童的生活， 他们的家庭，但这也将产生更大的社会影响，在经济和 教育成果。由于这两种单独的治疗方法都处于早期临床试验中，这 提案是加强儿科细胞治疗的下一个合乎逻辑的步骤。

Much progress has been made in the last 30 years to improve survival of children with CHD, but what was once a fatal condition is now a manageable long-term disease. Of these, children with Hypoplastic Left Heart Syndrome face the worst outcomes as they are left with a single ventricle (the right ventricle) that ultimately fails. These children are either left with long-term morbidity such as poor exercise tolerance, decreased executive function, and poor social skills. At the worst, they are placed on the transplant list where short-term survival in the highest need cohort is 50%, and grafts have a maximal longevity of roughly 12 years before needing a new heart. The goal of this study is to provide FDA-enabling data for a combination therapy of two Phase 1 FDA approved treatments; cardiac progenitor cells and decellularized porcine cardiac extracellular matrix. Cell therapy is promising in children, but similar to adult studies the cells do not persist for long and are transplanted to a diseased microenvironment. In 3 separate aims, we will examine the efficacy of this combined therapy in both immunocompromised and immune-competent rats, followed by large animal pig studies. These data will not only provide critical data for an FDA IND, but will also shed light on potential physiological mechanisms by which these therapies act. With congenital heart disease occurring in nearly 1% of all births and representing the most common birth defect, the potential impact of this study cannot be understated. Information gleaned from this study will not only improve the lives of nearly 40,000 children per year and their families, but it would also generate greater societal impact in terms of economic and educational outcomes. With both individual therapies under early clinical trials in humans, this proposal is the next logical step toward enhancing pediatric cell therapy.