title: Wound administration of M2-polarized macrophages does not improve murine cutaneous healing responses.
abstract: Macrophages play a crucial role in all stages of cutaneous wound healing responses and dysregulation of macrophage function can result in derailed wound repair. The phenotype of macrophages is influenced by the wound microenvironment and evolves during healing from a more pro-inflammatory (M1) profile in early stages, to a less inflammatory pro-healing (M2) phenotype in later stages of repair. The aim of the current study was to investigate the potential of exogenous administration of M2 macrophages to promote wound healing in an experimental mouse model of cutaneous injury. Bone marrow derived macrophages were stimulated in-vitro with IL-4 or IL-10 to obtain two different subsets of M2-polarized cells, M2a or M2c respectively. Polarized macrophages were injected into full-thickness excisional skin wounds of either C57BL/6 or diabetic db/db mice. Control groups were injected with non-polarized (M0) macrophages or saline. Our data indicate that despite M2 macrophages exhibit an anti-inflammatory phenotype in-vitro, they do not improve wound closure in wild type mice while they delay healing in diabetic mice. Examination of wounds on day 15 post-injury indicated delayed re-epithelialization and persistence of neutrophils in M2 macrophage treated diabetic wounds. Therefore, topical application of ex-vivo generated M2 macrophages is not beneficial and contraindicated for cell therapy of skin wounds.
authors: Department of Molecular Genetics, CARIM, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
authors: Nadine
authors: N
authors: Jetten
authors: Department of Plastic Surgery, NUTRIM, School for Nutrition, Toxicology & Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors: Nadia
authors: N
authors: Roumans
authors: Department of Molecular Genetics, CARIM, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands; Department of Pathology, CARIM, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
authors: Marion J
authors: MJ
authors: Gijbels
authors: Department of Gynecology, GROW, School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors: Andrea
authors: A
authors: Romano
authors: Department of Physiology, CARIM, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
authors: Mark J
authors: MJ
authors: Post
authors: Department of Molecular Genetics, CARIM, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
authors: Menno P J
authors: MP
authors: de Winther
authors: Department of Plastic Surgery, NUTRIM, School for Nutrition, Toxicology & Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors: Rene R W J
authors: RR
authors: van der Hulst
authors: Department of Plastic Surgery, NUTRIM, School for Nutrition, Toxicology & Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors: Sofia
authors: S
authors: Xanthoulea
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D017930:Genes, Reporter; D007150:Immunohistochemistry; D008264:Macrophages / Q000145:classification / Q000276:immunology / Q000378:metabolism; D051379:Mice; D012867:Skin / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D014945:Wound Healing