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Updated: May 17, 2026
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Assessment of Acute Wound Healing using the Dorsal Subcutaneous Polyvinyl Alcohol Sponge Implantation and Excisional Tail Skin Wound Models.
Published on: March 25, 2020
Embryonic stem cell-derived M2-like macrophages delay cutaneous wound healing
Daniela Dreymueller1, Bernd Denecke, Andreas Ludwig
1Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany. daniela.dreymueller@rwth-aachen.de
Summary
Topical application of embryonic stem cell-derived macrophages (ESDM) did not improve deep skin wound healing in mice. Despite an anti-inflammatory profile, ESDM unexpectedly delayed healing and increased scarring compared to bone marrow-derived macrophages.
Area of Science:
- Regenerative Medicine
- Wound Healing Biology
- Cell Therapy
Background:
- Adult skin wound repair typically results in scar formation, unlike scar-free healing in embryonic development.
- Macrophages play crucial roles in wound healing, with M2-like macrophages promoting tissue repair and scar reduction.
- Embryonic/fetal macrophages exhibit an M2-like phenotype, potentially contributing to scar-free healing.
Purpose of the Study:
- To investigate the efficacy of topical application of ex vivo generated embryonic stem cell-derived macrophages (ESDM) in improving deep skin wound healing in a murine model.
- To compare the effects of ESDM with bone marrow-derived macrophages (BMDM) on wound healing and scar formation.
Main Methods:
- Ex vivo generated embryonic stem cell-derived macrophages (ESDM) and bone marrow-derived macrophages (BMDM) were characterized for inflammatory and M2-like phenotypes.
- ESDM and BMDM were topically applied to deep skin wounds in mice.
- Wound healing rates and scar formation were assessed and compared between treatment groups (ESDM, BMDM, and cell-free control).
Main Results:
- ESDM exhibited reduced responsiveness to lipopolysaccharide, lower Toll-like receptor expression, and decreased bacterial phagocytosis, indicating an anti-inflammatory and M2-like phenotype compared to BMDM.
- Topical application of ESDM unexpectedly prolonged the healing time of deep skin wounds compared to both BMDM and cell-free treatment.
- Wounds treated with ESDM showed increased scar formation compared to wounds treated with BMDM or the cell-free control.
Conclusions:
- Topical application of ex vivo generated macrophages, including ESDM with an anti-inflammatory phenotype, is not a suitable cell therapy for promoting dermal wound healing.
- The anti-inflammatory or M2-like characteristics of macrophages do not necessarily translate to improved wound healing or reduced scarring in adult skin wounds.
- Further research is needed to understand the complex mechanisms regulating scar formation and identify effective cell-based therapies for regenerative wound healing.
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