Andreas Ludwig and Willi Jahnen-Dechent contributed equally.
Original Research-Basic Science
Embryonic stem cell–derived M2-like macrophages delay cutaneous wound healing
Article first published online: 5 NOV 2012
© 2012 by the Wound Healing Society
Wound Repair and Regeneration
Volume 21, Issue 1, pages 44–54, January-February 2013
How to Cite
Dreymueller, D., Denecke, B., Ludwig, A. and Jahnen-Dechent, W. (2013), Embryonic stem cell–derived M2-like macrophages delay cutaneous wound healing. Wound Repair and Regeneration, 21: 44–54. doi: 10.1111/j.1524-475X.2012.00858.x
- Issue published online: 8 JAN 2013
- Article first published online: 5 NOV 2012
- Manuscript Accepted: 13 AUG 2012
- Manuscript Received: 23 DEC 2011
- IZKF Aachen
In adults, repair of deeply injured skin wounds results in the formation of scar tissue, whereas in embryos wounds heal almost scar-free. Macrophages are important mediators of wound healing and secrete cytokines and tissue remodeling enzymes. In contrast to host defense mediated by inflammatory M1 macrophages, wound healing and tissue repair involve regulatory M2/M2-like macrophages. Embryonic/fetal macrophages are M2-like, and this may promote scar-free wound healing. In the present study, we asked whether atopical application of ex vivo generated, embryonic stem cell–derived macrophages (ESDM) improve wound healing in mice. ESDM were tested side by side with bone marrow–derived macrophages (BMDM). Compared to BMDM, ESDM resembled a less inflammatory and more M2-like macrophage subtype as indicated by their reduced responsiveness to lipopolysaccharide, reduced expression of Toll-like receptors, and reduced bacterial phagocytosis. Despite this anti-inflammatory phenotype in cell culture, ESDM prolonged the healing of deep skin wounds even more than BMDM. Healed wounds had more scar formation compared to wounds receiving BMDM or cell-free treatment. Our data indicate that atopical application of ex vivo generated macrophages is not a suitable cell therapy of dermal wounds.