Penn State College of Medicine, Pennsylvania State University, Hershey, PA, USA.
Northern Ontario School of Medicine, Ontario, CA, USA.
Stem Cell Res Ther. 2023 Oct 26;14(1):308. doi: 10.1186/s13287-023-03539-6.
Stem cell transplantation is an emerging therapy for severe cardiomyopathy, proffering stem cell recruitment, anti-apoptosis, and proangiogenic capabilities. Angiogenic cell precursors (ACP-01) are autologous, lineage-specific, cells derived from a multipotent progenitor cell population, with strong potential to effectively engraft, form blood vessels, and support tissue survival and regeneration.
This IRB approved outcome analysis reports upon 74 consecutive patients who failed medical management for severe cardiomyopathy, and were selected to undergo transcatheter intramyocardial or intracoronary implantation of ACP-01. Serious adverse events (SAEs) were reported. Cell analysis was conducted for each treatment. The left ventricular ejection fraction (LVEF) was measured by multi-gated acquisition scan (MUGA) or echocardiogram at 4 months ± 1.9 months and 12 months ± 5.5 months. Patients reported quality of life statements at 6 months (± 5.6 months).
Fifty-four of 74 patients met requirements for inclusion (48 males and five females; age 68.1 ± 11.3 years). The mean treatment cell number of 57 × 10 ACP-01 included 7.7 × 10 CD34 + and 21 × 10 CD31 + cells with 97.6% viability. SAEs included one death (previously unrecognized silent MI), ventricular tachycardia (n = 2) requiring cardioversion, and respiratory infection (n = 2). LVEF in the ischemic subgroup (n = 41) improved by 4.7% ± 9.7 from pre-procedure to the first follow-up (4 months ± 1.9 months) (p < 0.004) and by 7.2% ± 10.9 at final follow-up (n = 25) at average 12 months (p < 0.004). The non-ischemic dilated cardiomyopathy subgroup (n = 8) improved by 7.5% ± 6.0 at the first follow-up (p < 0.017) and by 12.2% ± 6.4 at final follow-up (p < 0.003, n = 6). Overall improvement in LVEF from pre-procedure to post-procedure was significant (Fisher's exact test p < 0.004). LVEF improvement was most marked in the patients with the most severe cardiomyopathy (LVEF < 20%) improving from a mean 14.6% ± 3.4% pre-procedurally to 28.4% ± 8% at final follow-up. Quality of life statements reflected improvement in 33/50 (66%), no change in 14/50 (28%), and worse in 3/50 (6%).
Transcatheter implantation of ACP-01 for cardiomyopathy is safe and improves LVEF in the setting of ischemic and non-ischemic cardiomyopathy. The results warrant further investigation in a prospective, blinded, and controlled clinical study.
IRB from Genetic Alliance #APC01-001, approval date July 25, 2022. Cardiomyopathy is common and associated with high mortality. Stem cell transplantation is an emerging therapy. Angiogenic cell precursors (ACP-01) are lineage-specific endothelial progenitors, with strong potential for migration, engraftment, angiogenesis, and support of tissue survival and regeneration. A retrospective outcomes analysis of 53 patients with ischemic and non-ischemic dilated cardiomyopathy undergoing transcatheter implantation of ACP-01 demonstrated improvements in the left ventricular ejection fraction of 7.2% ± 10.9 (p < 0.004) and 12.2% ± 6.4, respectively, at 12 months (± 5) follow-up. Quality of life statements reflected improvement in 33/50 (66%) patients.
干细胞移植是一种新兴的治疗严重心肌病的方法，具有招募干细胞、抗细胞凋亡和促血管生成的能力。血管生成细胞前体 (ACP-01) 是自体、谱系特异性的细胞，来源于多能祖细胞群体，具有有效定植、形成血管和支持组织存活和再生的强大潜力。
本 IRB 批准的结果分析报告了 74 例连续的严重心肌病患者，这些患者经药物治疗失败，选择接受 ACP-01 的经皮心肌内或冠状动脉内移植。报告了严重不良事件 (SAE)。对每个治疗进行细胞分析。左心室射血分数 (LVEF) 通过多门控采集扫描 (MUGA) 或超声心动图在 4 个月±1.9 个月和 12 个月±5.5 个月进行测量。患者在 6 个月（±5.6 个月）时报告生活质量声明。
74 例患者中，54 例符合纳入要求（48 名男性和 5 名女性；年龄 68.1±11.3 岁）。包括 7.7×10 CD34+和 21×10 CD31+细胞在内的 57×10 ACP-01 治疗细胞的平均数量为 57×10 ACP-01，细胞活力为 97.6%。SAE 包括一例死亡（先前未被识别的无症状心肌梗死）、室性心动过速（n=2）需要电复律和呼吸感染（n=2）。缺血性亚组（n=41）的 LVEF 在术前至第一次随访（4 个月±1.9 个月）时提高了 4.7%±9.7（p<0.004），在最后一次随访（n=25）时提高了 7.2%±10.9，平均为 12 个月（p<0.004）。非缺血性扩张型心肌病亚组（n=8）在第一次随访时提高了 7.5%±6.0（p<0.017），在最后一次随访时提高了 12.2%±6.4（p<0.003，n=6）。从术前到术后 LVEF 的总体改善具有统计学意义（Fisher 精确检验 p<0.004）。LVEF 的改善在最严重的心肌病患者（LVEF<20%）中最为显著，从术前的平均 14.6%±3.4%提高到最后一次随访时的 28.4%±8%。生活质量声明反映了 33/50（66%）患者的改善，14/50（28%）患者无变化，3/50（6%）患者恶化。
经皮植入 ACP-01 治疗心肌病是安全的，并可改善缺血性和非缺血性心肌病患者的 LVEF。结果表明，需要在一项前瞻性、盲法、对照的临床研究中进一步研究。
IRB 来自 Genetic Alliance #APC01-001，批准日期 2022 年 7 月 25 日。心肌病很常见，与高死亡率相关。干细胞移植是一种新兴的治疗方法。血管生成细胞前体（ACP-01）是谱系特异性内皮祖细胞，具有很强的迁移、定植、血管生成以及支持组织存活和再生的潜力。对 53 例接受 ACP-01 经皮植入的缺血性和非缺血性扩张型心肌病患者的回顾性结果分析表明，左心室射血分数分别提高了 7.2%±10.9（p<0.004）和 12.2%±6.4，在 12 个月（±5）随访时。生活质量声明反映了 33/50（66%）患者的改善。
