人 CD16 单核细胞 (hCD16 Ms) 具有促血管生成特性。我们评估了 hCD16 Ms 在猪心肌梗塞 (MI) 模型中的可行性、安全性和有效性。共有 27 头雌性大白猪通过再灌注和心脏磁共振 (CMR) 进行了 MI。五天后，动物接受心肌内注射 hCD16 Ms 的生理盐水 (n = 13) 或仅生理盐水 (n = 14)。 hCD16 Ms 选自白细胞锥体。可行性/安全性终点包括注射部位损伤、恶性心律失常、癌症、血肿、左心室（LV）扩张、肌钙蛋白释放和下游器官损伤。共同主要疗效结果包括 CMR 注射后 30 天的左室疤痕和射血分数 (LVEF)。免疫组织化学包括新血管生成、纤维化、肌成纤维细胞标记物和炎症。由于无法治疗的恶性心律失常或肺损伤，四只动物在注射前被排除。中位细胞数和活力分别为 4875 万和 87%。使用hCD16女士没有可行性/安全性问题。左心室疤痕减少了14.5gr（从25.45±8.24到10.8±3.4 gr；-55%）和6.4gr（从18.83±5.06到12.4±3.9gr；-55%）和6.4gr（从18.83±5.06到12.4±3.9gr；-55%）。 hCD16 Ms 组和对照组分别为 -30% (p = 0.015)。各组之间的 30 天 LVEF 没有差异，但 hCD16 Ms 组内预先指定的亚分析显示，接受较高细胞剂量的亚组中 LVEF 高出 2.8%，LV 疤痕低 1.9gr。在 hCD16 Ms 组中观察到新生血管生成、肌成纤维细胞和 IL-6 的组织水平较高，而 TGF-β 的水平较低。在急性 MI 中使用 hCD16 Ms 是可行、安全的，并且与减少左心室疤痕大小、增加组织有关注射后 30 天，新生血管生成、肌成纤维细胞和 IL-6 水平以及促纤维化 TGF-β 水平降低。较高的细胞剂量可能会增加 LVEF 效果，同时减少疤痕大小，但这需要在未来的研究中进行验证。© 2024 Ascione、Bruno、Johnson、Sammut、Bond、Lopez-Baz、Deutsch、Bailey、Chiribiri、Patel、Baker 和 Modarai。

Human CD16+ monocytes (hCD16+ Ms) have proangiogenic properties. We assessed the feasibility, safety and efficacy of hCD16+ Ms in a porcine model of myocardial infarction (MI).A total of 27 female Large White pigs underwent MI with reperfusion and cardiac magnetic resonance (CMR). Five days later, animals received intramyocardial injections of hCD16+ Ms in saline (n = 13) or saline only (n = 14). hCD16+ Ms were selected from leucocyte cones. Feasibility/safety endpoints included injury at injected sites, malignant arrhythmias, cancer, haematoma, left ventricular (LV) dilatation, troponin release and downstream organ injury. Co-primary efficacy outcome included LV scar and ejection fraction (LVEF) at 30-day post-injections by CMR. Immunohistochemistry included neo-angiogenesis, fibrosis, markers of myofibroblast and inflammation. Four animals were excluded before injections due to untreatable malignant arrhythmias or lung injury. Median cell number and viability were 48.75 million and 87%, respectively. No feasibility/safety concerns were associated with the use of hCD16+ Ms. The LV scar dropped by 14.5gr (from 25.45 ± 8.24 to 10.8 ± 3.4 gr; -55%) and 6.4gr (from 18.83 ± 5.06 to 12.4 ± 3.9gr; -30%) in the hCD16+ Ms and control groups, respectively (p = 0.015). The 30-day LVEF did not differ between groups, but a prespecified sub-analysis within the hCD16+ Ms group showed that LVEF was 2.8% higher and LV scar 1.9gr lower in the subgroup receiving a higher cell dose. Higher tissue levels of neo-angiogenesis, myofibroblast and IL-6 and lower levels of TGF-β were observed in the hCD16+ Ms group.The use of hCD16+ Ms in acute MI is feasible, safe and associated with reduced LV scar size, increased tissue levels of neo-angiogenesis, myofibroblasts and IL-6 and reduced pro-fibrotic TGF-β at 30-day post-injections. A higher cell dose might increase the LVEF effect while reducing scar size, but this warrants validation in future studies.© 2024 Ascione, Bruno, Johnson, Sammut, Bond, Lopez-Baz, Deutsch, Bailey, Chiribiri, Patel, Baker and Modarai.