Safety profile of autologous macrophage therapy for liver cirrhosis
Open accessAbstract
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 10 7, 10 8 or up to 10 9 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.
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During 12 months of follow-up after autologous macrophage transplantation, 70 adverse events were documented, 44% were considered related to transplantation, and none had a CTCAE severity grading over 2.
“During 12 months of follow-up, 70 AEs were documented, with 44% considered related to the transplantation, but none of these AEs had a Common Terminology Criteria for Adverse Events (CTCAE) severity grading over 2.”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [22]
The Safety outcomes section reports 70 adverse events during one year of follow-up and says 56% were unrelated to the investigational product, supporting the cited 44% related figure. The Discussion limits the CTCAE grade ≤2 finding to events possibly related to the product; it does not establish that none of all 70 events exceeded grade 2. Page numbers are unavailable in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn patients with liver cirrhosis, up to 1×10^9 in vitro expanded autologous bone marrow-derived macrophages were administered through a peripheral vein.
“in vitro expanded autologous BMDMs respectively through a peripheral vein [22].”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [22]
The Introduction and Method of cell production describe autologous macrophages made by culturing monocytes collected from patients’ blood by leukapheresis, then infused peripherally in patients with cirrhosis. The Discussion reports a maximum-achieved dose of 0.8×10^9 cells. The paper does not describe the administered cells as bone marrow-derived macrophages or establish that they were expanded in culture rather than differentiated there. (LLM, conf=0.88)
Experimental — accuracy not yet measuredRecent clinical trials provided evidence that administration of autologous macrophage therapy for liver fibrosis is safe, although the nature of these trials precluded efficacy assessment.
“recent clinical trials have provided evidence that the administration of autologous macrophage therapy for liver fibrosis is safe, although the nature of these trials precluded efficacy assessment (52, 53).”
From Impaired TIM4-mediated efferocytosis by liver macrophages contributes to fibrosis in metabolic dysfunction–associated steatohepatitis (2025) · cites this paper as [52]
Phase I studies demonstrated that macrophage infusion was safe and well-tolerated, and showed improvement in some serum biomarkers after treatment (C3M, PRO-C3, and ELF).
“Phase I studies demonstrated that macrophage infusion was safe and well-tolerated, and even showed improvement in some serum biomarkers after treatment (C3M, PRO-C3, and ELF) (176).”
From Targeting macrophages in liver fibrosis (2026) · cites this paper as [176]
A reduction of MELD scores was observed in six of nine patients 90 days following macrophage infusion, and in seven of nine patients one year post-infusion.
“A reduction of MELD scores was observed in six of the nine patients 90 days following macrophage infusion, and in seven of the nine patients one year post-infusion.”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [22]
Non-invasive measures of liver cirrhosis, such as serological markers of type-III collagen turnover, improved at day 90 after macrophage infusion.
“Furthermore, the non-invasive measures of LC, such as serological markers of type-III collagen turnover, improved at day 90.”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [22]
A phase I trial (Moroni et al., 2019) demonstrated that reinfusing autologous MDMs into cirrhosis patients is safe and led to observed improvements in MELD score and liver stiffness.
“A phase I trial (Moroni et al., 2019) first demonstrated that reinfusing autologous monocyte-derived macrophages (MDMs) into cirrhosis patients is safe and led to observed improvements in Model for End-Stage Liver Disease (MELD) score and liver stiffness (74).”
From Macrophage duality in liver diseases: heterogeneity, plasticity, and the quest for precision therapeutics (2026) · cites this paper as [74]
A Phase I clinical trial injecting autologous macrophages that express markers of tissue repair and inflammation resolution showed an improvement in liver function and reduction of fibrosis markers.
“The feasibility of the approach was further demonstrated by a Phase I clinical trial that injected autologous macrophages that express markers of tissue repair and inflammation resolution and showed an improvement in liver function and reduction of fibrosis markers (118).”
From Immunoregulation of Liver Fibrosis: New Opportunities for Antifibrotic Therapy (2024) · cites this paper as [118]
In a proof-of-concept trial, apheresis-derived autologous CD14+ monocytes were differentiated ex vivo into a restorative phenotype; a single injection of different doses appeared safe and was associated with a slight reduction in MELD score.
“In this proof-of-concept trial, apheresis-derived autologous CD14+ monocytes were differentiated ex vivo into a restorative phenotype (CD14+, high 25F9, CD206, CD163 and CD169). The single injection of different doses of these macrophages appeared safe and was associated with a (slight) reduction in the model of end-stage liver disease score.151”
From An integrated view of anti-inflammatory and antifibrotic targets for the treatment of NASH (2023) · cites this paper as [151]
A phase I trial in nine patients with compensated cirrhosis showed that macrophage therapy was feasible.
“The feasibility of such an approach was shown in a phase I clinical trial including nine patients with compensated cirrhosis.151”
From An integrated view of anti-inflammatory and antifibrotic targets for the treatment of NASH (2023) · cites this paper as [151]
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- Authors
- Moroni, F., Dwyer, B. J., Graham, C., Pass, C., Bailey, L., Ritchie, L., Mitchell, D., Glover, A., Laurie, A., Doig, S., Hargreaves, E., Fraser, A. R., Turner, M. L., Campbell, J. D. M., McGowan, N. W. A., Barry, J., Moore, J. K., Hayes, P. C., Leeming, D. J., Nielsen, M. J., Musa, K., Fallowfield, J. A., & Forbes, S. J.
- Affiliations
- MRC Centre for Regenerative Medicine (GB)
- University of Edinburgh (GB)
- Scottish National Blood Transfusion Service (GB)
- Guy's Hospital (GB)
- Centre for Inflammation Research (GB)
- Nordic Bioscience (Denmark) (DK)
- Corresponding author
- Forbes, Stuart J.
- ORCID
- Venue
- Nature Medicine
- Published
- 2019-10
- Volume
- 25
- Issue
- 10
- Pages
- 1560-1565
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2977548937
- Cited by
- 202
- References
- 35
- Citations by year
- 2026: 16 · 2025: 35 · 2024: 38 · 2023: 25 · 2022: 26 · 2021: 40 · 2020: 20 · 2019: 1 · 2017: 1
- FWCI
- 13.86
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Aberdeen University Research Archive (Aberdeen University) (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- RCUK | Medical Research Council (MR/M007588/1)
- RCUK | MRC | Medical Research Foundation (MR/M007588/1)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- liver cirrhosis, liver fibrosis, leukapheresis, safety and tolerability, dose-limiting toxicity, macrophage activation syndrome, ascites
- MeSH terms
- Aged, Dose-Response Relationship, Immunologic, Female, Humans, Liver, Liver Cirrhosis, Liver Regeneration, Macrophages, Male, Middle Aged, End Stage Liver Disease, Cell- and Tissue-Based Therapy
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