Acetaminophen (APAP)-induced injury is a common clinical phenomenon that not only occurs in a dose-dependent manner but also occurs in some idiosyncratic individuals in a dose-independent manner. APAP overdose generally results in acute liver injury via the initiation of oxidative stress, endoplasmic reticulum (ER) stress, autophagy, liver inflammation, and microcirculatory dysfunction. Liver transplantation is the only effective strategy for treating APAP-induced liver failure, but liver transplantation is inhibited by scarce availability of donor liver grafts, acute graft rejection, lifelong immunosuppression, and unbearable costs. Currently, N-acetylcysteine (NAC) effectively restores liver functions early after APAP intake, but it does not protect against APAP-induced injury at the late stage. An increasing number of animal studies have demonstrated that mesenchymal stem cells (MSCs) significantly attenuate acute liver injury through their migratory capacity, hepatogenic differentiation, immunoregulatory capacity, and paracrine effects in acute liver failure (ALF). In this review, we comprehensively discuss the mechanisms of APAP overdose-induced liver injury and current therapies for treating APAP-induced liver injury. We then comprehensively summarize recent studies about transplantation of MSC and MSC derivatives for treating APAP-induced liver injury. We firmly believe that MSCs and their derivatives will effectively promote liver regeneration and liver injury repair in APAP overdose-treated animals and patients. To this end, MSC-based therapies may serve as an effective strategy for patients who are waiting for liver transplantation during the early and late stages of APAP-induced ALF in the near future.

中文翻译：

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间充质干细胞及其衍生物的移植有效地促进了肝的再生，从而减轻了对乙酰氨基酚引起的肝损伤。

对乙酰氨基酚（APAP）诱导的损伤是一种常见的临床现象，不仅以剂量依赖性的方式发生，而且在某些特异个体中以剂量依赖性的方式发生。APAP过量通常会通过引发氧化应激，内质网（ER）应激，自噬，肝脏炎症和微循环功能障碍而导致急性肝损伤。肝移植是治疗APAP引起的肝衰竭的唯一有效策略，但由于供体肝移植物供应稀少，急性移植物排斥，终生免疫抑制和难以承受的费用，肝移植受到抑制。目前，N-乙酰半胱氨酸（NAC）可在APAP摄入后早期有效地恢复肝功能，但不能在晚期抵抗APAP诱导的损伤。越来越多的动物研究表明，间充质干细胞（MSC）通过迁移能力，肝细胞分化，免疫调节能力和急性肝衰竭（ALF）的旁分泌作用显着减轻了急性肝损伤。在这篇综述中，我们全面讨论了APAP过量引起的肝损伤的机制以及目前治疗APAP引起的肝损伤的疗法。然后，我们全面总结了有关MSC和MSC衍生物移植治疗APAP所致肝损伤的最新研究。我们坚信，MSCs及其衍生物将有效地促进APAP过量治疗的动物和患者的肝脏再生和肝损伤修复。为此，