Lim Rebecca, Hodge Alexander, Moore Gregory, Wallace Euan M, Sievert William
The Ritchie Centre, Hudson Institute of Medical Research, ClaytonVIC, Australia.
Department of Obstetrics and Gynaecology, Monash University, MelbourneVIC, Australia.
Front Pharmacol. 2017 Aug 23;8:549. doi: 10.3389/fphar.2017.00549. eCollection 2017.
Liver cirrhosis is the 6th leading cause of death in adults aged 15-59 years in high-income countries. For many who progress to cirrhosis, the only prospect for survival is liver transplantation. While there is some indication that mesenchymal stem cells may be useful in reversing established liver fibrosis, there are limitations to their widespread use - namely their rarity, the need for extensive serial passaging and the associated potential for genomic instability and cellular senescence. To this end, we propose the use of allogeneic amnion epithelial cells. This clinical trial will assess the safety of intravenously delivered allogeneic human amnion epithelial cells (hAECs) in patients with compensated liver cirrhosis. This will also provide clinical data that will inform phases 2 and 3 clinical trials with the ultimate goal of developing hAECs as a therapeutic option for patients with cirrhosis who are at significant risk of disease progression. We will recruit 12 patients with compensated cirrhosis, based on their hepatic venous pressure gradient, for a dose escalation study. Patients will be closely monitored in the first 24 h post-infusion, then via daily telephone interviews until clinical assessment on day 5. Long term follow up will include standard liver tests, transient elastography and hepatic ultrasound. Ethics approval was obtained from Monash Health for this trial 16052A, "A Pilot Study Evaluating the Safety of Intravenously Administered Human Amnion Epithelial Cells for the Treatment of Liver Fibrosis, A First in Adult Human Study." The trial will be conducted in accordance to Monash Health Human Ethics guidelines. Outcomes from this study will be disseminated in the form of conference presentations and submission to a peer reviewed journal. This trial has been registered on the Australian and New Zealand Clinical Trials Registry ACTRN12616000437460.
在高收入国家，肝硬化是15至59岁成年人中第六大主要死因。对于许多进展为肝硬化的患者来说，生存的唯一希望是肝移植。虽然有迹象表明间充质干细胞可能有助于逆转已形成的肝纤维化，但其广泛应用存在局限性——即其稀缺性、需要大量连续传代以及相关的基因组不稳定和细胞衰老的可能性。为此，我们提议使用异体羊膜上皮细胞。这项临床试验将评估静脉注射异体人羊膜上皮细胞（hAECs）对代偿期肝硬化患者的安全性。这也将提供临床数据，为2期和3期临床试验提供参考，最终目标是将hAECs开发成为疾病进展风险高的肝硬化患者的一种治疗选择。我们将根据肝静脉压力梯度招募12名代偿期肝硬化患者进行剂量递增研究。患者在输注后的前24小时将受到密切监测，然后通过每日电话访谈进行监测，直至第5天进行临床评估。长期随访将包括标准肝功能检查、瞬时弹性成像和肝脏超声检查。本试验“评估静脉注射人羊膜上皮细胞治疗肝纤维化安全性的初步研究，成人首例研究”已获得莫纳什健康中心的伦理批准，批准号为16052A。该试验将按照莫纳什健康中心人类伦理指南进行。本研究的结果将以会议报告的形式发布，并提交给同行评审期刊。该试验已在澳大利亚和新西兰临床试验注册中心注册，注册号为ACTRN12616000437460。
