DataSheet1_Human Umbilical Cord Blood Mononuclear Cells Ameliorate CCl4-Induced Acute Liver Injury in Mice via Inhibiting Inflammatory Responses and Upregulating Peripheral Interleukin-22.pdf

Background: Human umbilical cord blood mononuclear cells (hUCBMNCs) show therapeutic effects on many inflammatory diseases. The deterioration of acute liver injury is attributed to excessive inflammatory responses triggered by damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs). Whether hUCBMNCs treatment is a promising strategy for acute liver injury/failure needs to be investigated.Methods: Liver injury mice induced by PAMPs, DAMPs, or DAMPs plus PAMPs were developed. DAMPs included CCl4 (carbon tetrachloride), APAP (acetaminophen), and ConA (Concanavalin A). PAMPs included Klebsiella pneumoniae (K.P.) and Salmonella typhimurium (S. Typhimurium). DAMP plus PAMP-induced liver injury was developed by sequential CCl4 and K.P. administration. hUCBMNCs were injected intravenously.Results: hUCBMNCs significantly prolonged mice survival time in DAMP plus PAMP-induced liver failure but had no benefit in bacteria-infected mice. hUCBMNCs significantly alleviated hepatic necrosis post CCl4/ConA insult. In CCl4-induced acute liver injury, peripheral levels of interleukin (IL)-22 were upregulated and liver regeneration was enhanced after treating with hUCBMNCs at 48h. The levels of p62 and LC3B-II, autophagy markers, were also upregulated in the hUCBMNC-treated group.Conclusion: hUCBMNCs as a kind of cell therapeutic strategy could attenuate acute liver injury in mice, which is executed by enhancing autophagy and regeneration in the liver via inhibiting inflammatory responses and upregulating peripheral IL-22.

背景：人脐带血单个核细胞（hUCBMNCs）对多种炎症性疾病展现出显著的疗效。急性肝损伤的恶化归因于由损伤相关分子模式（DAMPs）和病原体相关分子模式（PAMPs）触发的过度炎症反应。hUCBMNCs治疗是否为急性肝损伤/衰竭的潜在策略尚需进一步研究。方法：通过PAMPs、DAMPs或DAMPs与PAMPs的联合作用诱导了肝损伤小鼠模型。DAMPs包括四氯化碳（CCl4）、对乙酰氨基酚（APAP）和刀豆蛋白A（ConA）。PAMPs包括肺炎克雷伯菌（K.P.）和鼠伤寒沙门氏菌（S. Typhimurium）。通过先后给予CCl4和K.P.建立了DAMPs加PAMPs诱导的肝损伤模型。hUCBMNCs通过静脉注射给予。结果：hUCBMNCs在DAMPs加PAMPs诱导的肝衰竭小鼠中显著延长了生存时间，但在细菌感染小鼠中未显示出任何益处。hUCBMNCs显著减轻了CCl4/ConA损伤后的肝坏死。在CCl4诱导的急性肝损伤中，给予hUCBMNCs处理48小时后，外周白细胞介素（IL）-22水平上调，肝再生增强。在hUCBMNCs处理组中，自噬标志物p62和LC3B-II水平也显著上调。结论：作为一种细胞治疗策略，hUCBMNCs能够减轻小鼠的急性肝损伤，通过抑制炎症反应并上调外周IL-22水平，增强肝脏的自噬和再生作用。