Cryopreserved human alternatively activated macrophages promote resolution of acetaminophen-induced liver injury in mouse
Abstract 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 rapidl...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
|
| Series: | npj Regenerative Medicine |
| Online Access: | https://doi.org/10.1038/s41536-025-00393-3 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832585986688679936 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Maria Elena Candela |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-558266651d8d4e43b0d143a19e0bd3c0 |
| institution | Kabale University |
| issn | 2057-3995 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Regenerative Medicine |
| spelling | doaj-art-558266651d8d4e43b0d143a19e0bd3c02025-01-26T12:19:04ZengNature Portfolionpj Regenerative Medicine2057-39952025-01-0110111510.1038/s41536-025-00393-3Cryopreserved human alternatively activated macrophages promote resolution of acetaminophen-induced liver injury in mouseMaria Elena Candela0Melisande Addison1Rhona Aird2Tak-Yung Man3Jennifer A. Cartwright4Candice Ashmore-Harris5Alastair M. Kilpatrick6Philip J. Starkey Lewis7Anna Drape8Mark Barnett9Donna Mitchell10Colin McLean11Neil McGowan12Marc Turner13James W. Dear14Stuart J. Forbes15Centre for Regenerative Medicine, The Institute for Regeneration and Repair, University of EdinburghCentre for Regenerative Medicine, The Institute for Regeneration and Repair, University of EdinburghCentre for Regenerative Medicine, The Institute for Regeneration and Repair, University of EdinburghCentre for Regenerative Medicine, The Institute for Regeneration and Repair, University of EdinburghCentre for Regenerative Medicine, The Institute for Regeneration and Repair, University of EdinburghCentre for Regenerative Medicine, The Institute for Regeneration and Repair, University of EdinburghCentre for Regenerative Medicine, The Institute for Regeneration and Repair, University of EdinburghCentre for Regenerative Medicine, The Institute for Regeneration and Repair, University of EdinburghScottish National Blood Transfusion Service (SNBTS), The Jack Copland Centre, Heriot-Watt Research ParkScottish National Blood Transfusion Service (SNBTS), The Jack Copland Centre, Heriot-Watt Research ParkScottish National Blood Transfusion Service (SNBTS), The Jack Copland Centre, Heriot-Watt Research ParkScottish National Blood Transfusion Service (SNBTS), The Jack Copland Centre, Heriot-Watt Research ParkScottish National Blood Transfusion Service (SNBTS), The Jack Copland Centre, Heriot-Watt Research ParkScottish National Blood Transfusion Service (SNBTS), The Jack Copland Centre, Heriot-Watt Research ParkCentre for Precision Cell Therapy for the Liver, Lothian Health Board, Queens Medical Research InstituteCentre for Regenerative Medicine, The Institute for Regeneration and Repair, University of EdinburghAbstract 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.https://doi.org/10.1038/s41536-025-00393-3 |
| spellingShingle | 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 Cryopreserved human alternatively activated macrophages promote resolution of acetaminophen-induced liver injury in mouse npj Regenerative Medicine |
| title | Cryopreserved human alternatively activated macrophages promote resolution of acetaminophen-induced liver injury in mouse |
| title_full | Cryopreserved human alternatively activated macrophages promote resolution of acetaminophen-induced liver injury in mouse |
| title_fullStr | Cryopreserved human alternatively activated macrophages promote resolution of acetaminophen-induced liver injury in mouse |
| title_full_unstemmed | Cryopreserved human alternatively activated macrophages promote resolution of acetaminophen-induced liver injury in mouse |
| title_short | Cryopreserved human alternatively activated macrophages promote resolution of acetaminophen-induced liver injury in mouse |
| title_sort | cryopreserved human alternatively activated macrophages promote resolution of acetaminophen induced liver injury in mouse |
| url | https://doi.org/10.1038/s41536-025-00393-3 |
| work_keys_str_mv | AT mariaelenacandela cryopreservedhumanalternativelyactivatedmacrophagespromoteresolutionofacetaminopheninducedliverinjuryinmouse AT melisandeaddison cryopreservedhumanalternativelyactivatedmacrophagespromoteresolutionofacetaminopheninducedliverinjuryinmouse AT rhonaaird cryopreservedhumanalternativelyactivatedmacrophagespromoteresolutionofacetaminopheninducedliverinjuryinmouse AT takyungman cryopreservedhumanalternativelyactivatedmacrophagespromoteresolutionofacetaminopheninducedliverinjuryinmouse AT jenniferacartwright cryopreservedhumanalternativelyactivatedmacrophagespromoteresolutionofacetaminopheninducedliverinjuryinmouse AT candiceashmoreharris cryopreservedhumanalternativelyactivatedmacrophagespromoteresolutionofacetaminopheninducedliverinjuryinmouse AT alastairmkilpatrick cryopreservedhumanalternativelyactivatedmacrophagespromoteresolutionofacetaminopheninducedliverinjuryinmouse AT philipjstarkeylewis cryopreservedhumanalternativelyactivatedmacrophagespromoteresolutionofacetaminopheninducedliverinjuryinmouse AT annadrape cryopreservedhumanalternativelyactivatedmacrophagespromoteresolutionofacetaminopheninducedliverinjuryinmouse AT markbarnett cryopreservedhumanalternativelyactivatedmacrophagespromoteresolutionofacetaminopheninducedliverinjuryinmouse AT donnamitchell cryopreservedhumanalternativelyactivatedmacrophagespromoteresolutionofacetaminopheninducedliverinjuryinmouse AT colinmclean cryopreservedhumanalternativelyactivatedmacrophagespromoteresolutionofacetaminopheninducedliverinjuryinmouse AT neilmcgowan cryopreservedhumanalternativelyactivatedmacrophagespromoteresolutionofacetaminopheninducedliverinjuryinmouse AT marcturner cryopreservedhumanalternativelyactivatedmacrophagespromoteresolutionofacetaminopheninducedliverinjuryinmouse AT jameswdear cryopreservedhumanalternativelyactivatedmacrophagespromoteresolutionofacetaminopheninducedliverinjuryinmouse AT stuartjforbes cryopreservedhumanalternativelyactivatedmacrophagespromoteresolutionofacetaminopheninducedliverinjuryinmouse |