Ahmed Mustafa M, Meece Lauren E, Handberg Eileen M, Gonzalez Rafael, Guo Yi, Lou Xiwei, Pepine Carl J
Division of Cardiovascular Medicine, University of Florida College of Medicine, Gainesville, Florida.
RESTEM LLC, Corona, California.
JHLT Open. 2023 Dec 9;3:100037. doi: 10.1016/j.jhlto.2023.100037. eCollection 2024 Feb.
Left ventricular assist device (LVAD) implantation improves survival in advanced heart failure. Despite this, angiodysplastic bleeding complications remain a significant driver of costs as well as morbidity. Mechanisms implicated in post-LVAD implant bleeding include the dysregulation of angiogenic factors seen in this population. The present pilot study evaluates the safety of umbilical cord lining stem cells (ULSCs) in LVAD recipients while exploring any early evidence of efficacy to improve bleeding.
In a 3 + 3 design, 9 patients received an intravenous (IV) infusion of ULSCs at escalating doses. The primary endpoint was safety and tolerability, secondary exploratory outcomes included antibodies against hemoglobin to quantify the amount of blood in stool without the need for dietary restriction.
The primary safety and tolerability outcomes were met as no infusion-related adverse events or toxic responses were observed. There was no sensitization after administration of ULSCs as assessed by panel reactive antibody. An increase in angiopoietin-1 levels and a decrease in angiopoietin-2 levels from baseline to 30 days were observed in 4 patients. Quantitative Faecal Immunochemical Test suggested a decrease in the mean blood content of stool from baseline to 30 days.
In this first-ever IV administration of ULSCs in LVAD patients, infusion was noted to be safe and tolerable and did not cause immune sensitization. Half of the patients were noted to have angiogenic stabilization, and there was a trend toward decreasing amounts of blood noted in the stool, suggesting an early signal of efficacy.
植入左心室辅助装置（LVAD）可提高晚期心力衰竭患者的生存率。尽管如此，血管发育异常出血并发症仍然是成本和发病率的重要驱动因素。LVAD植入术后出血的相关机制包括该人群中血管生成因子的失调。本初步研究评估了脐带衬里干细胞（ULSCs）在LVAD接受者中的安全性，同时探索其改善出血效果的早期证据。
采用3+3设计，9例患者接受了递增剂量的ULSCs静脉输注。主要终点是安全性和耐受性，次要探索性结果包括针对血红蛋白的抗体，以在无需饮食限制的情况下量化粪便中的出血量。
达到了主要安全性和耐受性结果，因为未观察到与输注相关的不良事件或毒性反应。通过群体反应性抗体评估，ULSCs给药后未出现致敏现象。4例患者从基线到30天观察到血管生成素-1水平升高，血管生成素-2水平降低。定量粪便免疫化学检测表明，从基线到30天，粪便中的平均血液含量有所下降。
在首次对LVAD患者进行ULSCs静脉给药的研究中，发现输注是安全且可耐受的，不会引起免疫致敏。注意到一半的患者血管生成稳定，并且粪便中血液量有减少的趋势，这表明有早期疗效信号。
