Peripheral infusion of human umbilical cord mesenchymal stem cells rescues acute liver failure lethality in monkeys
Peripheral infusion of human umbilical cord mesenchymal stem cells rescues acute liver failure lethality in monkeys
复制标题
人脐带间充质干细胞的外周输注可挽救猴子急性肝衰竭的死亡
DOI：
10.1186/s13287-019-1184-2
复制
发表时间：
2019-03-12
影响因子：
7.5
通讯作者：
Shi, Yujun
中科院分区：
文献类型：
--
作者：
Guo, Gang;Zhuang, Xiang;Shi, Yujun
背景急性肝功能衰竭(ALF)是一种复杂的临床综合征，死亡率高，肝移植是唯一的治疗选择。间充质干细胞的治疗已显示出治疗急性肝功能衰竭的一种潜在选择。然而，由于缺乏随机的临床试验和大量的非人类灵长类动物研究，有必要在临床上评估其有效性和安全性。方法采用外周输注人脐血间充质干细胞(Huc-MSCs)治疗猕猴，观察Huc-MSCs在急性肝功能衰竭过程中的调控作用。结论单核细胞来源的IL-6在急性肝功能衰竭的发生和发展中起重要作用，Huc-MSC治疗可通过抑制单核细胞的活化来阻断炎症级联反应的发展。早期的Huc-MSC治疗破坏了炎症级联反应的发展，表明了一种治疗急性肝功能衰竭的潜在临床解决方案。
BackgroundAcute liver failure (ALF) is a complicated clinical syndrome associated with high mortality, with liver transplantation as the only treatment option. Treatment of mesenchymal stem cells has shown a potential therapeutic option for acute liver failure. However, the lack of random clinical trials and large non-human primate studies makes it necessary to assess the efficacy and safety in the clinic.MethodsWe treated the monkeys with peripheral delivery of human umbilical MSCs (hUC-MSCs) and investigated the role of hUC-MSCs in modulating the progress of acute liver failure.ResultsThe use of early peripheral infusion of human umbilical cord MSC infusion did not improve liver regeneration or modulate adaptive immunity. However, it significantly suppressed the hepatic aggregation and maturation of circulating monocytes and their IL-6 secretion, greatly improving liver histology, systemic homeostasis, and survival.ConclusionsOur study reveals the critical role of monocyte-derived IL-6 in initiating and accelerating acute liver failure and hUC-MSC treatment can disrupt the development of the inflammatory cascade by inhibiting monocyte activation. Early hUC-MSC treatment disrupts the development of the inflammatory cascade, indicating a potential clinical solution for acute liver failure.