Evaluating Early and Late Functional, Immune and Angiogenic Responses to Injected Cardiac Fibroblast Derived Matrix in a Myocardial Infarction Model

摘要 Cellular Logistics（CL）在生物材料方面的创新提供了一种解决方案，可以限制和逆转 心肌梗死（MI）。每年有超过805，000名美国人患有心肌梗死（MI）。生存 MI后的改善主要是由于改善了旨在加速冠状动脉粥样硬化的急性护理系统， 动脉再灌注然而，大的和/或反复的MI是常见的，并且仍然是心力衰竭的主要原因 (HF)住院和死亡。预防心肌梗死后心力衰竭的标准治疗包括阻断心肌梗死后心力衰竭的药物。 适应不良的神经激素途径，但这些药物是部分有效的，并不是普遍耐受。 对于那些进展到终末期HF的人，心脏移植可能是挽救生命的;然而， 患者的需求远远超过了供体器官的需求， 相当可观这种日益增长的未满足的需求推动了支架疗法的概念，以修复衰竭的心脏。 CL提出的SBIR的产物将是心脏成纤维细胞衍生的细胞外基质（CF-ECM）， 可注射脱细胞生物材料作为独立MI治疗。来源于人心脏成纤维细胞的培养 (CF)CF-ECM具有独特的蛋白质组成，其主要由不溶性纤连蛋白， 已知细胞外基质蛋白在心脏愈合中具有重要作用。CF-ECM被认为是 通过影响愈合反应，特别是通过调节免疫系统和诱导新的 血管生长CF-ECM在注入心脏时也附着在心肌上， 治疗益处。该SBIR的长期目标是将CF-ECM开发为独立的治疗方法， 加速心肌梗死后愈合，从而限制梗死扩展、心肌梗死后有害的重塑， 进展为HF。我们假设CF-ECM的早期作用是调节免疫系统， 抗炎状态，并增加受损心肌中的血管生成。而且我们 假设CF-ECM是安全且改善心脏功能和减少适应不良的重构，从而 减少HF的进展。CL已确定CF-ECM具有重要的商业机会： 美国每年约有805，000名MI患者，CF-ECM的估计市场规模约为20亿美元/年， 预计2021年至2026年的复合年增长率为2.7%。CL的创新生物材料有可能限制MI后 这是对抗迅速发展的HF流行病的重要一步。

Abstract Cellular Logistics’ (CL) innovation in biomaterials offers a solution to limit and reverse damage caused by myocardial infarction (MI). Over 805,000 Americans suffer a myocardial infarction (MI) each year. Survival following MI has improved largely due to improved acute systems of care designed to accelerate coronary artery reperfusion. However, large and/or repeated MIs are common and remain a major cause of heart failure (HF) hospitalizations and death. Standard therapy to prevent post-MI HF involve medications that block maladaptive neurohormonal pathways, but these drugs are partially effective and are not universally tolerated. For those who progress to end-stage HF, cardiac transplantation may be lifesaving; however, the supply of donor organs is far outpaced by patient need and complications associated with transplantation are substantial. This growing unmet need has fueled the concept of scaffold therapies to repair the failing heart. The product of CL’s proposed SBIR will be the cardiac fibroblast derived extracellular matrix (CF-ECM), an injectable acellular biomaterial as standalone MI therapy. Derived from the culture of human cardiac fibroblasts (CF), CF-ECM has a unique protein composition that is composed primarily of insoluble fibronectin, an extracellular matrix protein that is known to have an important role in cardiac healing. CF-ECM is thought to work by influencing the healing response, specifically, by modulating the immune system and inducing new blood vessel growth. CF-ECM also attaches to the myocardium when injected into the heart, boosting its therapeutic benefits. The long-term goal of this SBIR is to develop CF-ECM as a standalone therapeutic to accelerate post-MI healing, thereby limiting infarct expansion, post-MI deleterious remodeling, and the progression to HF. We hypothesize that the early effects of CF-ECM are to modulate the immune system to an anti-inflammatory state and increases angiogenesis in the damaged myocardium. Furthermore, we hypothesize that CF-ECM is safe and improve cardiac function and reduce maladaptive remodeling, thereby reducing the progression to HF. CL has determined that CF-ECM has significant commercial opportunity: With ~805,000 MI patients in the US each year, the estimated market size for CF-ECM is ~$2B/year with an estimated CAGR of 2.7% between 2021 and 2026. CL’s innovative biomaterial has the potential to limit post-MI damage—an important step toward confronting the burgeoning HF epidemic.