Safety profile of autologous macrophage therapy for liver cirrhosis

Francesca Moroni, Benjamin J Dwyer, Catriona Graham, Chloe Pass, Laura Bailey, Lisa Ritchie, Donna Mitchell, Alison Glover, Audrey Laurie, Stuart Doig, Emily Hargreaves, Alasdair R Fraser, Marc L Turner, John D M Campbell, Neil W A McGowan, Jacqueline Barry, Joanna K Moore, Peter C Hayes, Diana J Leeming, Mette J Nielsen & 3 others Kishwar Musa, Jonathan A Fallowfield, Stuart J Forbes*

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Therapies to reduce liver fibrosis and stimulate organ regeneration are urgently needed. We conducted a first-in-human, phase 1 dose-escalation trial of autologous macrophage therapy in nine adults with cirrhosis and a Model for End-Stage Liver Disease (MELD) score of 10-16 (ISRCTN 10368050). Groups of three participants received a single peripheral infusion of 107, 108 or up to 109 cells. Leukapheresis and macrophage infusion were well tolerated with no transfusion reactions, dose-limiting toxicities or macrophage activation syndrome. All participants were alive and transplant-free at one year, with only one clinical event recorded, the occurrence of minimal ascites. The primary outcomes of safety and feasibility were met. This study informs and provides a rationale for efficacy studies in cirrhosis and other fibrotic diseases.

Original languageEnglish
Pages (from-to)1560-1565
Number of pages6
JournalNature Medicine
Volume25
Early online date7 Oct 2019
DOIs
Publication statusPublished - Oct 2019

Fingerprint

Macrophages
Liver Cirrhosis
Liver
Macrophage Activation Syndrome
Fibrosis
Leukapheresis
Safety
End Stage Liver Disease
Ascites
Regeneration
Transplants
Toxicity
Therapeutics
Chemical activation
Transfusion Reaction

Keywords

  • regeneration
  • translational research
  • DIAGNOSIS
  • MARKER
  • DISEASE
  • INJURY
  • FUNCTIONAL-CHARACTERIZATION
  • CELL THERAPY
  • DUCTULAR REACTIONS
  • TRANSPLANTATION

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Moroni, F., Dwyer, B. J., Graham, C., Pass, C., Bailey, L., Ritchie, L., ... Forbes, S. J. (2019). Safety profile of autologous macrophage therapy for liver cirrhosis. Nature Medicine, 25, 1560-1565. https://doi.org/10.1038/s41591-019-0599-8

Safety profile of autologous macrophage therapy for liver cirrhosis. / Moroni, Francesca; Dwyer, Benjamin J; Graham, Catriona; Pass, Chloe; Bailey, Laura; Ritchie, Lisa; Mitchell, Donna; Glover, Alison; Laurie, Audrey; Doig, Stuart; Hargreaves, Emily; Fraser, Alasdair R; Turner, Marc L; Campbell, John D M; McGowan, Neil W A; Barry, Jacqueline; Moore, Joanna K; Hayes, Peter C; Leeming, Diana J; Nielsen, Mette J; Musa, Kishwar; Fallowfield, Jonathan A; Forbes, Stuart J.

In: Nature Medicine, Vol. 25, 10.2019, p. 1560-1565.

Research output: Contribution to journalArticle

Moroni, F, Dwyer, BJ, Graham, C, Pass, C, Bailey, L, Ritchie, L, Mitchell, D, Glover, A, Laurie, A, Doig, S, Hargreaves, E, Fraser, AR, Turner, ML, Campbell, JDM, McGowan, NWA, Barry, J, Moore, JK, Hayes, PC, Leeming, DJ, Nielsen, MJ, Musa, K, Fallowfield, JA & Forbes, SJ 2019, 'Safety profile of autologous macrophage therapy for liver cirrhosis', Nature Medicine, vol. 25, pp. 1560-1565. https://doi.org/10.1038/s41591-019-0599-8
Moroni, Francesca ; Dwyer, Benjamin J ; Graham, Catriona ; Pass, Chloe ; Bailey, Laura ; Ritchie, Lisa ; Mitchell, Donna ; Glover, Alison ; Laurie, Audrey ; Doig, Stuart ; Hargreaves, Emily ; Fraser, Alasdair R ; Turner, Marc L ; Campbell, John D M ; McGowan, Neil W A ; Barry, Jacqueline ; Moore, Joanna K ; Hayes, Peter C ; Leeming, Diana J ; Nielsen, Mette J ; Musa, Kishwar ; Fallowfield, Jonathan A ; Forbes, Stuart J. / Safety profile of autologous macrophage therapy for liver cirrhosis. In: Nature Medicine. 2019 ; Vol. 25. pp. 1560-1565.
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