Candela Maria Elena, Addison Melisande, Aird Rhona, Man Tak-Yung, Cartwright Jennifer A, Ashmore-Harris Candice, Kilpatrick Alastair M, Starkey Lewis Philip J, Drape Anna, Barnett Mark, Mitchell Donna, McLean Colin, McGowan Neil, Turner Marc, Dear James W, Forbes Stuart J
Centre for Regenerative Medicine, The Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, UK.
The Royal (Dick) School of Veterinary Studies and the Roslin Institute, University of Edinburgh, Edinburgh, UK.
NPJ Regen Med. 2025 Jan 22;10(1):5. doi: 10.1038/s41536-025-00393-3.
Acute liver failure is a rapidly progressing, life-threatening condition most commonly caused by an overdose of acetaminophen (paracetamol). The antidote, N-acetylcysteine (NAC), has limited efficacy when liver injury is established. If acute liver damage is severe, liver failure can rapidly develop with associated high mortality rates. We have previously demonstrated that alternatively, activated macrophages are a potential therapeutic option to reverse acute liver injury in pre-clinical models. In this paper, we present data using cryopreserved human alternatively activated macrophages (hAAMs)-which represent a potential, rapidly available treatment suitable for use in the acute setting. In a mouse model of APAP-induced injury, peripherally injected cryopreserved hAAMs reduced liver necrosis, modulated inflammatory responses, and enhanced liver regeneration. hAAMs were effective even when administered after the therapeutic window for NAC. This cell therapy approach represents a potential treatment for APAP overdose when NAC is ineffective because liver injury is established.
急性肝衰竭是一种迅速进展、危及生命的病症，最常见的病因是对乙酰氨基酚（扑热息痛）过量服用。当肝损伤已经形成时，解毒剂N - 乙酰半胱氨酸（NAC）的疗效有限。如果急性肝损伤严重，肝衰竭会迅速发展，伴有高死亡率。我们之前已经证明，在临床前模型中，活化的巨噬细胞是逆转急性肝损伤的一种潜在治疗选择。在本文中，我们展示了使用冷冻保存的人交替活化巨噬细胞（hAAMs）的数据——这代表了一种潜在的、可快速获得的治疗方法，适用于急性情况。在对乙酰氨基酚诱导损伤的小鼠模型中，外周注射冷冻保存的hAAMs可减少肝坏死、调节炎症反应并增强肝脏再生。即使在NAC治疗窗之后给药，hAAMs仍然有效。当NAC因肝损伤已经形成而无效时，这种细胞治疗方法代表了对乙酰氨基酚过量服用的一种潜在治疗方法。
