title: Autologous Adipose Stromal Cells Seeded onto a Human Collagen Matrix for Dermal Regeneration in Chronic Wounds: Clinical Proof of Concept.
abstract: BACKGROUND
  Nonhealing wounds are unable to integrate skin autografts by avascular and fibrotic dermal tissue. Adipose-derived stromal cells can improve the local environment of the wound bed by angiogenesis and immunomodulation. This work aimed to develop a biological dressing made of adipose-derived stromal cells onto a human acellular collagen matrix.
  
  
  METHODS
  Adipose-derived stromal cells were isolated from human adipose tissue (n = 8). In vitro, the genetic stability during early and late passages (1, 4, 10, and 16) and vascular endothelial growth factor (VEGF) secretion were assessed. Adipose-derived stromal cell adhesion and spreading on collagen matrix were preliminarily studied. In vivo tumorigenicity, angiogenesis, and tissue oxygenation were assessed after implantation of the construct in nude rats (n = 10). The biological dressing was manufactured and implanted in three patients with chronic wounds.
  
  
  RESULTS
  In vitro, aneuploidies, but no clonal transformation, were detected up to late cellular passages. VEGF was secreted more during hypoxia (0.1% oxygen) than during normoxia (21% oxygen). Adipose-derived stromal cells can adhere and spread on the scaffold within 18 to 20 days. No tumor development occurred 3 months after implantation in immunocompromised rats. Vessel counts and tissue oxygenation were higher after adipose-derived stromal cell implantation. In patients, granulation tissue was found (276 percent of vessel density), followed by epithelialization or split-thickness skin engraftment up to 22 months after implantation.
  
  
  CONCLUSIONS
  Implantation of adipose-derived stromal cells seeded onto human acellular collagen matrix (biological dressing) represents a promising therapy for nonhealing wounds, offering improvement in dermal angiogenesis and remodeling. This therapy using autologous stromal cells is safe, without significant genetic alterations after in vitro expansion.
authors.affiliation: Brussels, Belgium From the Endocrine Cell Therapy Unit, Center of Tissue/Cell Therapy, Institut de Recherche Expérimentale et Clinique, Plastic and Reconstructive Surgery Unit, Louvain Drug Research Institute, Biomedical Magnetic Resonance Research Unit, Center for Human Genetics and Human Molecular Genetics, de Duve Institute, Cliniques Universitaires Saint-Luc, Cardiovascular Research Unit, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain.
authors.forename: Aurore
authors.initials: A
authors.lastname: Lafosse
authors.forename: Céline
authors.initials: C
authors.lastname: Desmet
authors.forename: Najima
authors.initials: N
authors.lastname: Aouassar
authors.forename: Wivine
authors.initials: W
authors.lastname: André
authors.forename: Marie-Sophie
authors.initials: MS
authors.lastname: Hanet
authors.forename: Christophe
authors.initials: C
authors.lastname: Beauloye
authors.forename: Romain
authors.initials: R
authors.lastname: Vanwijck
authors.forename: Hélène A
authors.initials: HA
authors.lastname: Poirel
authors.forename: Bernard
authors.initials: B
authors.lastname: Gallez
authors.forename: Denis
authors.initials: D
authors.lastname: Dufrane
mesh_terms: D017667:Adipocytes / Q000637:transplantation*; D000818:Animals; D001684:Biological Dressings / Q000706:statistics & numerical data*; D002908:Chronic Disease; D018920:Coculture Techniques / Q000379:methods; D003094:Collagen / Q000502:physiology*; D006801:Humans; D018919:Neovascularization, Physiologic / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000502:physiology; D012680:Sensitivity and Specificity; D017768:Skin, Artificial; D017154:Stromal Cells / Q000637:transplantation*; D014182:Transplantation, Autologous; D014463:Ultrasonography; D014945:Wound Healing / Q000502:physiology; D014947:Wounds and Injuries / Q000000981:diagnostic imaging*
chemical_list: D003094:Collagen