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

评估心肌梗死模型中注射的心肌成纤维细胞衍生基质的早期和晚期功能、免疫和血管生成反应

• 批准号: 10384742
• 负责人: ERIC GARY SCHMUCK
• 金额: $ 33.71万
• 依托单位: CELLULAR LOGISTICS INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-19 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10384742
• 关键词: Acute; Adult; Aftercare; Age; American; Anti-Inflammatory Agents; Biocompatible Materials; Biomedical Engineering; Blood Vessels; Cardiac; Cardiac Myocytes; Cardiac health; Cessation of life; Clinical Trials; Coronary artery; EFRAC; Echocardiography; Epidemic; Extracellular Matrix; Extracellular Matrix Proteins; Fibroblasts; Fibronectins; Fibrosis; Goals; Growth; Heart; Heart Transplantation; Heart failure; Histologic; Histology; Hospitalization; Hour; Human; Hypertrophy; IL6 gene; Immune; Immune response; Immune system; In Vitro; Incidence; Infarction; Inflammatory; Inflammatory Response; Injectable; Injections; Knowledge; Legal patent; Logistics; Measures; Mesenchymal Stem Cells; Modeling; Mus; Myocardial; Myocardial Infarction; Myocardium; Natural regeneration; Organ Donor; Outcome; PECAM1 gene; Pathway interactions; Patients; Persons; Pharmaceutical Preparations; Phase; Phenotype; Pilot Projects; Placebo Control; Population; Proteins; Regenerative Medicine; Reperfusion Therapy; Risk; Role; Small Business Innovation Research Grant; Systolic Pressure; Testing; Therapeutic; Thick; Time; Tissues; Transplantation; Trichrome stain method; United States; Vascular Endothelial Growth Factors; Work; angiogenesis; arginase; cardioprotection; care systems; commercial application; cytokine; design; effective therapy; healing; heart dimension/size; heart function; human old age (65+); improved; in vivo; innovation; macrophage; mortality; myocardial damage; neutrophil; novel; pressure; prevent; primary endpoint; product development; recruit; reduce symptoms; regenerative; repaired; response; scaffold; secondary endpoint

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.

抽象的 Cellular Logistics (CL) 在生物材料方面的创新提供了一种解决方案，可以限制和扭转因以下原因造成的损害： 每年有超过 805,000 名美国人患有心肌梗塞 (MI)。 由于旨在加速冠状动脉粥样硬化的急性护理系统的改进，心肌梗死后的情况得到了很大程度的改善 然而，大面积和/或重复的心肌梗死很常见，并且仍然是心力衰竭的主要原因。 (心力衰竭) 住院和死亡 预防心梗后心力衰竭的标准治疗包括阻断药物。 适应不良的神经激素途径，但这些药物是部分有效的，并且不被普遍耐受。 对于进展为终末期心力衰竭的患者，心脏移植可能可以挽救生命，但心脏移植的供应可能会受到影响。 供体器官的供应远远超过患者的需求，并且与移植相关的并发症也很严重 这种不断增长的未满足的需求催生了修复衰竭心脏的支架疗法的概念。 CL 提出的 SBIR 的产品将是心脏成纤维细胞衍生的细胞外基质（CF-ECM），一种 可注射的非细胞生物材料作为独立的心肌梗死疗法，源自人类心脏成纤维细胞的培养物。 (CF)，CF-ECM 具有独特的蛋白质成分，主要由不溶性纤连蛋白组成，纤连蛋白是一种 已知在心脏愈合中具有重要作用的细胞外基质蛋白。 通过影响愈合反应来发挥作用，特别是通过调节免疫系统和诱导新的免疫系统 当注入心脏时，CF-ECM 也会附着在心肌上，促进其生长。 该 SBIR 的长期目标是开发 CF-ECM 作为一种独立的治疗方法。 加速 MI 后愈合，从而限制梗塞扩展、MI 后有害重塑以及 我们发现 CF-ECM 的早期作用是将免疫系统调节为 HF。 抗炎状态并增加受损心肌的血管生成。 CF-ECM 是安全的，可以改善心脏功能并减少适应不良重构，从而 减少 CL 的进展已确定 CF-ECM 具有重大的商业机会： 美国每年约有 805,000 名 MI 患者，CF-ECM 的估计市场规模约为每年 2B 美元， 预计 2021 年至 2026 年复合年增长率为 2.7%。CL 的创新生物材料有潜力限制心肌梗死后的发生 损害——应对迅速蔓延的心衰流行的重要一步。