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Updated: May 31, 2026
Isolation of Human BAMBIhighMFGE8high Umbilical Cord-Derived Mesenchymal Stromal Cells
Published on: January 10, 2025
Damage-associated molecular patterns (DAMPs) and mesenchymal stem cells: a matter of attraction and excitement
Vito Pistoia1, Lizzia Raffaghello
1Laboratory of Oncology, G. Departmental of Experimental and Laboratory Medicine, Gaslini Institute, Genoa, Italy. vitopistoia@ospedale-gaslini.ge.it
Abstract:
Necrotic cell death is a typical feature of solid tumors leading to the release of necrotic products, also known as damage-associated molecular patterns (DAMPs), that enhance angiogenesis and prime the immune response. Among the DAMPs, particular attention has been focused on the DNA-binding molecule high-mobility group box 1 (HMGB-1) that can act as a chemoattractant and activator of granulocytes. Here, we discuss an article in this issue of the European Journal of Immunology that demonstrates that DAMPs promote both proliferation and trafficking of mesenchymal stem cells (MSCs), identifying HMGB-1 as a key factor in the regulation of these processes. Moreover, the study shows that DAMPs interfere with the expression of the immunosuppressive molecule indoleamine-2,3-dioxygenase in MSCs, and that the biological activity of HMGB-1 toward MSCs is abolished when HMGB-1 is oxidized. Based on the data from this, and other studies, we depict a model in which DAMPs released from necrotic tumor cells attract and stimulate local proliferation of MSCs that differentiate into tumor-associated fibroblasts promoting tumor growth and angiogenesis. Importantly, the hypoxic conditions of the tumor microenvironment may protect DAMPs from oxidation and thereby preserve their functionality.
Insights
Damage-associated molecular patterns (DAMPs) from necrotic tumors, particularly high-mobility group box 1 (HMGB-1), stimulate mesenchymal stem cell (MSC) proliferation and migration. Oxidized HMGB-1 loses its activity, suggesting a role for tumor hypoxia in maintaining DAMPs
Area of Science:
- Immunology
- Cancer Biology
- Stem Cell Biology
Background:
- Necrotic cell death in solid tumors releases damage-associated molecular patterns (DAMPs).
- High-mobility group box 1 (HMGB-1) is a key DAMP involved in immune responses and chemoattraction.
- Mesenchymal stem cells (MSCs) are implicated in tumor progression.
Purpose of the Study:
- To investigate the role of DAMPs, specifically HMGB-1, in regulating MSC proliferation and trafficking.
- To explore the impact of DAMPs on MSC immunosuppressive functions.
- To understand the influence of oxidation and tumor microenvironment on HMGB-1 activity.
Main Methods:
- Analysis of DAMPs' effects on MSC proliferation and migration.
- Assessment of HMGB-1's role in MSC regulation.
- Investigation of HMGB-1 oxidation status and its biological activity.
- Modeling the interplay between necrotic tumor cells, DAMPs, MSCs, and the tumor microenvironment.
Main Results:
- DAMPs, including HMGB-1, promote MSC proliferation and trafficking.
- HMGB-1 is identified as a key regulator of these MSC processes.
- DAMPs interfere with indoleamine-2,3-dioxygenase expression in MSCs.
- Oxidation of HMGB-1 abolishes its biological activity toward MSCs.
- Hypoxic tumor conditions may preserve DAMP functionality by preventing oxidation.
Conclusions:
- DAMPs released from necrotic tumors stimulate MSCs, promoting tumor growth and angiogenesis.
- HMGB-1 plays a critical role in DAMP-mediated MSC stimulation.
- MSCs differentiate into tumor-associated fibroblasts, contributing to tumor progression.
- Tumor microenvironment, particularly hypoxia, influences DAMP activity and function.
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