title: Cell recruitment by amnion chorion grafts promotes neovascularization.
abstract: BACKGROUND
  Nonhealing wounds are a significant health burden. Stem and progenitor cells can accelerate wound repair and regeneration. Human amniotic membrane has demonstrated efficacy in promoting wound healing, though the underlying mechanisms remain unknown. A dehydrated human amnion chorion membrane (dHACM) was tested for its ability to recruit hematopoietic progenitor cells to a surgically implanted graft in a murine model of cutaneous ischemia.
  
  
  METHODS
  dHACM was subcutaneously implanted under elevated skin (ischemic stimulus) in either wild-type mice or mice surgically parabiosed to green fluorescent protein (GFP) + reporter mice. A control acellular dermal matrix, elevated skin without an implant, and normal unwounded skin were used as controls. Wound tissue was harvested and processed for histology and flow cytometric analysis.
  
  
  RESULTS
  Implanted dHACMs recruited significantly more progenitor cells compared with controls (*P < 0.05) and displayed in vivo SDF-1 expression with incorporation of CD34 + progenitor cells within the matrix. Parabiosis modeling confirmed the circulatory origin of recruited cells, which coexpressed progenitor cell markers and were localized to foci of neovascularization within implanted matrices.
  
  
  CONCLUSIONS
  In summary, dHACM effectively recruits circulating progenitor cells, likely because of stromal derived factor 1 (SDF-1) expression. The recruited cells express markers of "stemness" and localize to sites of neovascularization, providing a partial mechanism for the clinical efficacy of human amniotic membrane in the treatment of chronic wounds.
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, California.
authors.forename: Zeshaan N
authors.initials: ZN
authors.lastname: Maan
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, California.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Rennert
authors.affiliation: MiMedx Group, Inc., Marietta, Georgia.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Koob
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, California.
authors.forename: Michael
authors.initials: M
authors.lastname: Januszyk
authors.affiliation: Angiogenesis Foundation, Cambridge, Massachusetts.
authors.forename: William W
authors.initials: WW
authors.lastname: Li
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, California.
authors.forename: Geoffrey C
authors.initials: GC
authors.lastname: Gurtner
mesh_terms: D000650:Amnion / Q000637:transplantation*; D000818:Animals; D002823:Chorion / Q000637:transplantation*; D004195:Disease Models, Animal; D005260:Female; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D007511:Ischemia / Q000628:therapy*; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic; D010227:Parabiosis
keywords: Amniotic membrane; Chronic wounds; Hematopoietic progenitor cell; Neovascularization; Progenitor cell recruitment; SDF-1; dHACM