title: Embryonic stem cell-derived M2-like macrophages delay cutaneous wound healing.
abstract: 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.
authors.affiliation: Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany. daniela.dreymueller@rwth-aachen.de
authors.forename: Daniela
authors.initials: D
authors.lastname: Dreymueller
authors.forename: Bernd
authors.initials: B
authors.lastname: Denecke
authors.forename: Andreas
authors.initials: A
authors.lastname: Ludwig
authors.forename: Willi
authors.initials: W
authors.lastname: Jahnen-Dechent
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002921:Cicatrix / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000637:transplantation*; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation / Q000473:pathology / Q000628:therapy*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D012038:Regeneration; D012867:Skin / Q000473:pathology*; D014945:Wound Healing; D014947:Wounds and Injuries / Q000473:pathology / Q000628:therapy*