Zeng Yuting, Wu Zhenru, Chen Gen, Liu Guoqiang, Zhang Bo, Zhou Yongjie, Chen Menglin, Yao Rong, Shi Yujun
Liver Transplant Center Transplant Center and Key Laboratory of Transplant Engineering and Immunology NHC West China Hospital Sichuan University, Chengdu, China.
Institute of clinical Pathology West China Hospital Sichuan University, Chengdu, China.
Stem Cells Int. 2024 Jul 16;2024:4654912. doi: 10.1155/2024/4654912. eCollection 2024.
Using a toxin-induced lethal acute liver failure (ALF) monkey model, we have recently shown that early peripheral infusion of human umbilical cord mesenchymal stem cells (hUC-MSCs) can alleviate liver damage and improve animal survival by suppressing the activation of circulating monocytes and the subsequent cytokine storm. Here, we explored whether the administration of hUC-MSCs could still improve ALF when the cytokine storm is fully developed.
We treated ALF monkeys with peripheral delivery of hUC-MSCs at 48 hr after toxin challenge. Liver indices, histology, imaging, and animal survival were recorded and analyzed.
In our cohort study, we conducted and demonstrated that the infusion of hUC-MSCs significantly improved liver histology, effectively controlled inflammatory cytokine storms, and increased survival rates. Additionally, the administration of a higher dose of hUC-MSCs (2 × 10/monkey) yielded superior outcomes compared to a lower dose (1 × 10/monkey).
Treatment of hUC-MSCs can significantly improve the pathological and survival outcomes of ALF even when the cytokine storm has been fully developed, indicating a promising clinical solution for ALF.
我们最近利用毒素诱导的致死性急性肝衰竭（ALF）猴模型表明，早期外周输注人脐带间充质干细胞（hUC-MSCs）可通过抑制循环单核细胞的激活及随后的细胞因子风暴来减轻肝损伤并提高动物存活率。在此，我们探讨了在细胞因子风暴充分发展时，给予hUC-MSCs是否仍能改善急性肝衰竭。
在毒素攻击后48小时，我们通过外周给予hUC-MSCs治疗急性肝衰竭猴。记录并分析肝脏指标、组织学、影像学及动物存活率。
在我们的队列研究中，我们进行并证明输注hUC-MSCs可显著改善肝脏组织学，有效控制炎性细胞因子风暴，并提高存活率。此外，与较低剂量（1×10/猴）相比，给予较高剂量的hUC-MSCs（2×10/猴）产生了更好的结果。
即使细胞因子风暴已充分发展，hUC-MSCs治疗仍可显著改善急性肝衰竭的病理及存活结局，这表明其是一种有前景的急性肝衰竭临床解决方案。
