Cryopreserved human alternatively activated macrophages promote resolution of acetaminophen-induced liver injury in mouse
Acute liver failure (ALF) 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 N-acetylcysteine. This cell therapy approach represents a potential treatment for APAP overdose when NAC is ineffective because liver injury is established. Overall design: Liver tissue was taken from C57BL/6J mice for RNA sequencing. Mice were either untreated (control; n=3), or treated with 350 mg/kg APAP. APAP-treated animals were given either PBS vehicle (n=5) or hAAM cells (n=4).