Cryopreserved human alternatively activated macrophages promote resolution of acetaminophen-induced liver injury in mouse

Maria Elena Candela; Melisande Addison; Rhona Aird; Tak Yung Man; Jennifer A. Cartwright; Candice Ashmore-Harris; Alastair M. Kilpatrick; Philip J. Starkey Lewis; Anna Drape; Mark Barnett; Donna Mitchell; Colin McLean; Neil McGowan; Marc Turner; James W. Dear; Stuart J. Forbes

doi:10.1038/s41536-025-00393-3

Cryopreserved human alternatively activated macrophages promote resolution of acetaminophen-induced liver injury in mouse

Maria Elena Candela^*, Melisande Addison, Rhona Aird, Tak Yung Man, Jennifer A. Cartwright, Candice Ashmore-Harris, Alastair M. Kilpatrick, Philip J. Starkey Lewis, Anna Drape, Mark Barnett, Donna Mitchell, Colin McLean, Neil McGowan, Marc Turner, James W. Dear, Stuart J. Forbes

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Article number	5
Journal	npj Regenerative Medicine
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41536-025-00393-3
Publication status	Published - 22 Jan 2025

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10.1038/s41536-025-00393-3Licence: Creative Commons: Attribution (CC-BY)

candela et al., 2025_Marilena CandelaAccepted author manuscript, 25.3 MBLicence: Creative Commons: Attribution (CC-BY)
s41536-025-00393-3Final published version, 5.73 MBLicence: Creative Commons: Attribution (CC-BY)

Macrophage Therapy for Acute Liver failure (DPFS)
Forbes, S. (Principal Investigator), Forbes, S. (Principal Investigator), Dear, J. (Co-investigator), Dear, J. (Co-investigator) & Weir, C. (Co-investigator)
Medical Research Council
1/12/20 → 30/11/25
Project: Research

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Candela, M. E., Addison, M., Aird, R., Man, T. Y., Cartwright, J. A., Ashmore-Harris, C., Kilpatrick, A. M., Starkey Lewis, P. J., Drape, A., Barnett, M., Mitchell, D., McLean, C., McGowan, N., Turner, M., Dear, J. W., & Forbes, S. J. (2025). Cryopreserved human alternatively activated macrophages promote resolution of acetaminophen-induced liver injury in mouse. npj Regenerative Medicine, 10(1), Article 5. https://doi.org/10.1038/s41536-025-00393-3

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title = "Cryopreserved human alternatively activated macrophages promote resolution of acetaminophen-induced liver injury in mouse",

abstract = "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. ",

author = "Candela, {Maria Elena} and Melisande Addison and Rhona Aird and Man, {Tak Yung} and Cartwright, {Jennifer A.} and Candice Ashmore-Harris and Kilpatrick, {Alastair M.} and {Starkey Lewis}, {Philip J.} and Anna Drape and Mark Barnett and Donna Mitchell and Colin McLean and Neil McGowan and Marc Turner and Dear, {James W.} and Forbes, {Stuart J.}",

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doi = "10.1038/s41536-025-00393-3",

language = "English",

volume = "10",

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Candela, ME , Addison, M , Aird, R, Man, TY, Cartwright, JA, Ashmore-Harris, C , Kilpatrick, AM, Starkey Lewis, PJ, Drape, A, Barnett, M, Mitchell, D, McLean, C, McGowan, N, Turner, M, Dear, JW & Forbes, SJ 2025, 'Cryopreserved human alternatively activated macrophages promote resolution of acetaminophen-induced liver injury in mouse', npj Regenerative Medicine, vol. 10, no. 1, 5. https://doi.org/10.1038/s41536-025-00393-3

TY - JOUR

T1 - Cryopreserved human alternatively activated macrophages promote resolution of acetaminophen-induced liver injury in mouse

AU - Candela, Maria Elena

AU - Addison, Melisande

AU - Aird, Rhona

AU - Man, Tak Yung

AU - Cartwright, Jennifer A.

AU - Ashmore-Harris, Candice

AU - Kilpatrick, Alastair M.

AU - Starkey Lewis, Philip J.

AU - Drape, Anna

AU - Barnett, Mark

AU - Mitchell, Donna

AU - McLean, Colin

AU - McGowan, Neil

AU - Turner, Marc

AU - Dear, James W.

AU - Forbes, Stuart J.

PY - 2025/1/22

Y1 - 2025/1/22

N2 - 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.

AB - 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.

U2 - 10.1038/s41536-025-00393-3

DO - 10.1038/s41536-025-00393-3

M3 - Article

SN - 2057-3995

VL - 10

JO - npj Regenerative Medicine

JF - npj Regenerative Medicine

IS - 1

M1 - 5

ER -

Cryopreserved human alternatively activated macrophages promote resolution of acetaminophen-induced liver injury in mouse

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Macrophage Therapy for Acute Liver failure (DPFS)

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