title: Arteriogenesis in murine adipose tissue is contingent on CD68+/CD206+macrophages.
abstract: The surgical transfer of skin, fat, and/or muscle from a donor site to a recipient site within the same patient is a widely performed procedure in reconstructive surgeries. A surgical pretreatment strategy that is intended to increase perfusion in the flap, termed "flap delay," is a commonly employed technique by plastic surgeons prior to flap transplantation. Here, we explored whether CD68+/CD206+macrophages are required for arteriogenesis within the flap by performing gain-of-function and loss-of-function studies in a previously published flap delay murine model.
  
  
  
  Local injection of M2-polarized macrophages into the flap resulted in an increase in collateral vessel diameter. Application of a thin biomaterial film loaded with a pharmacological agent (FTY720), which has been previously shown to recruit CD68+/CD206+macrophages to remodeling tissue, increased CD68+/CD206+cell recruitment and collateral vessel enlargement. Conversely, when local macrophage populations were depleted within the inguinal fat pad via clodronate liposome delivery, we observed fewer CD68+cells accompanied by diminished collateral vessel enlargement.
  
  
  
  Our study underscores the importance of macrophages during microvascular adaptations that are induced by flap delay. These studies suggest a mechanism for a translatable therapeutic target that may be used to enhance the clinical flap delay procedure.
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Seaman
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA.
authors.forename: Yiqi
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Plastic Surgery, University of Virginia, Charlottesville, VA, USA.
authors.forename: Chris A
authors.initials: CA
authors.lastname: Campbell
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA.|Department of Plastic Surgery, University of Virginia, Charlottesville, VA, USA.
authors.forename: Shayn M
authors.initials: SM
authors.lastname: Peirce
mesh_terms: D000273:Adipose Tissue / Q000098:blood supply*; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D001158:Arteries / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*; D002465:Cell Movement / Q000187:drug effects; D000068876:Fingolimod Hydrochloride / Q000008:administration & dosage / Q000494:pharmacology; D037181:Lectins, C-Type / Q000032:analysis; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000032:analysis; D051379:Mice; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000032:analysis; D013524:Surgical Flaps / Q000098:blood supply* / Q000637:transplantation; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000068876:Fingolimod Hydrochloride; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; C081026:CD68 protein, mouse; D000097382:CD68 Molecule
keywords: adipose; arteriogenesis; collateral vessel; macrophage