Alginate microencapsulated human hepatocytes for the treatment of acute liver failure in children
Alginate microencapsulated human hepatocytes for the treatment of acute liver failure in children
复制标题
DOI：
10.1016/j.jhep.2019.12.002
复制
发表时间：
2020-05-01
影响因子：
25.7
通讯作者：
Mitry, Ragai R.
中科院分区：
文献类型：
--
作者：
Dhawan, Anil;Chaijitraruch, Nataruks;Mitry, Ragai R.
背景和目标：肝移植（LT）是急性肝功能衰竭（ALF）患者最有效的治疗方法，但受到手术风险和终身免疫抑制需求的限制。藻酸盐微囊化人肝细胞移植是一个有吸引力的选择比全肝替代。肝细胞微珠移植的安全性和有效性已在动物模型中得到证实。我们报告我们的经验，这种疗法在儿童ALF治疗的命名patientbasis.Methods：临床级人肝细胞微珠（HMBs）和空微珠进行了测试，在免疫功能正常的健康大鼠。随后，8名等待合适的同种异体移植物进行LT的ALF儿童接受了HMB腹腔内移植。我们监测并发症的过程中，评估宿主的免疫反应和残余功能的检索HMBs，无论是自发的原生肝再生后，或在LT的时间。结果：HMBs在健康大鼠的腹膜内移植是安全的，并保留合成和解毒功能，而不需要免疫抑制。随后，8例ALF儿童接受了HMB（4例新生儿血色病，2例病毒感染和2例输注时原因不明的儿童），中位年龄为14.5天，范围为1天至6岁。手术耐受性良好，无并发症。在8例患儿中，4例避免了LT，3例在干预后成功桥接至LT。输注后检索的HMB（在LT的时间）结构完整，无宿主细胞粘附，并含有活的肝细胞与保存functions.Conclusion：结果表明，在ALF.Lay总结的儿童HMB输注的可行性和安全性：急性肝功能衰竭的儿童是一种罕见的，但破坏性的条件。肝移植是最有效的治疗方法，但它有几个重要的局限性。肝细胞（肝细胞）移植是一个有吸引力的选择，因为许多患者只需要短期的肝脏支持，而他们自己的肝脏恢复。包封在藻酸盐珠中的人肝细胞可以执行肝脏的功能，而藻酸盐涂层保护细胞免受免疫攻击。在此，我们证明了这些珠子移植在急性肝功能衰竭儿童中是安全可行的。(c)2019由Elsevier B.V.代表欧洲肝脏研究协会发表。
Background & Aims: Liver transplantation (LT) is the most effective treatment for patients with acute liver failure (ALF), but is limited by surgical risks and the need for life-long immunosuppression. Transplantation of microencapsulated human hepatocytes in alginate is an attractive option over whole liver replacement. The safety and efficacy of hepatocyte microbead transplantation have been shown in animal models. We report our experience of this therapy in children with ALF treated on a named-patient basis.Methods: Clinical grade human hepatocyte microbeads (HMBs) and empty microbeads were tested in immunocompetent healthy rats. Subsequently, 8 children with ALF, who were awaiting a suitable allograft for LT, received intraperitoneal transplantation of HMBs. We monitored complications of the procedure, assessing the host immune response and residual function of the retrieved HMBs, either after spontaneous native liver regeneration or at the time of LT.Results: Intraperitoneal transplantation of HMBs in healthy rats was safe and preserved synthetic and detoxification functions, without the need for immunosuppression. Subsequently, 8 children with ALF received HMBs (4 neonatal haemochromatosis, 2 viral infections and 2 children with unknown cause at time of infusion) at a median age of 14.5 days, range 1 day to 6 years. The procedure was well tolerated without complications. Of the 8 children, 4 avoided LT while 3 were successfully bridged to LT following the intervention. HMBs retrieved after infusions (at the time of LT) were structurally intact, free of host cell adherence and contained viable hepatocytes with preserved functions.Conclusion: The results demonstrate the feasibility and safety of an HMB infusion in children with ALF.Lay summary: Acute liver failure in children is a rare but devastating condition. Liver transplantation is the most effective treatment, but it has several important limitations. Liver cell (hepatocyte) transplantation is an attractive option, as many patients only require short-term liver support while their own liver recovers. Human hepatocytes encapsulated in alginate beads can perform the functions of the liver while alginate coating protects the cells from immune attack. Herein, we demonstrated that transplantation of these beads was safe and feasible in children with acute liver failure. (c) 2019 Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.