There are nearly 65 million people with chronic heart failure (CHF) globally, with no treatment directed at the pathologic cause of the disease, the loss of functioning cardiomyocytes. We have an allogeneic cardiac patch comprised of cardiomyocytes and human fibroblasts on a bioresorbable matrix. This patch increases blood flow to the damaged heart and improves left ventricular (LV) function in an immune competent rat model of ischemic CHF. After 6 months of treatment in an immune competent Yucatan mini swine ischemic CHF model, this patch restores LV contractility without constrictive physiology, partially reversing maladaptive LV and right ventricular remodeling, increases exercise tolerance, without inducing any cardiac arrhythmias or a change in myocardial oxygen consumption. Digital spatial profiling in mice with patch placement 3 weeks after a myocardial infarction shows that the patch induces a CD45^pos immune cell response that results in an infiltration of dendritic cells and macrophages with high expression of macrophages polarization to the anti-inflammatory reparative M2 phenotype. Leveraging the host native immune system allows for the potential use of immunomodulatory therapies for treatment of chronic inflammatory diseases not limited to ischemic CHF.

全球有近 6500 万人患有慢性心力衰竭 (CHF)，但没有针对该疾病的病理原因（功能性心肌细胞丧失）的治疗方法。我们有一个同种异体心脏补片，由位于生物可吸收基质上的心肌细胞和人成纤维细胞组成。在免疫功能正常的缺血性 CHF 大鼠模型中，该贴片可增加流向受损心脏的血流量并改善左心室 (LV) 功能。在免疫能力强的尤卡坦半岛小型猪缺血性 CHF 模型中治疗 6 个月后，该贴片可恢复左心室收缩力，而不会造成生理收缩，部分逆转适应不良的左心室和右心室重塑，提高运动耐量，不会引起任何心律失常或心肌耗氧量的变化。心肌梗塞后 3 周放置贴片的小鼠的数字空间分析表明，贴片诱导 CD45 ^pos免疫细胞反应，导致树突状细胞和巨噬细胞浸润，巨噬细胞高表达，极化为抗炎修复 M2 表型。利用宿主天然免疫系统可以使用免疫调节疗法来治疗慢性炎症性疾病，而不仅限于缺血性CHF。