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.

摘要