title: Mesenchymal stromal cells for cutaneous wound healing in a rabbit model: pre-clinical study applicable in the pediatric surgical setting.
abstract: OBJECTIVE
  Mesenchymal stromal cells (MSCs) expanded in vitro have been proposed as a potential therapy for congenital or acquired skin defects in pediatrics. The aim of this pre-clinical study was to investigate the effects of intradermal injections of MSC in experimental cutaneous wound repair comparing allogeneic and autologous adipose stem cells (ASCs) and autologous bone marrow-mesenchymal stromal cells (BM-MSCs).
  
  
  METHODS
  Mesenchymal stromal cells were in vitro expanded from adipose and BM tissues of young female New Zealand rabbits. MSCs were characterized for plastic adhesion, surface markers, proliferation and differentiation capacity. When an adequate number of cells (ASCs 10 × 10(6) and BM-MSCs 3 × 10(6), because of their low rate of proliferation) was reached, two skin wounds were surgically induced in each animal. The first was topically treated with cell infusions, the second was used as a control. The intradermal inoculation included autologous or allogeneic ASCs or autologous BM-MSCs. For histological examination, animals were sacrificed and wounds were harvested after 11 and 21 days of treatment.
  
  
  RESULTS
  Rabbit ASCs were isolated and expanded in vitro with relative abundance, cells expressed typical surface markers (CD49e, CD90 and CD29). Topically, ASC inoculation provided more rapid wound healing than BM-MSCs and controls. Improved re-epithelization, reduced inflammatory infiltration and increased collagen deposition were observed in biopsies from wounds treated with ASCs, with the best result in the autologous setting. ASCs also improved restoration of skin architecture during wound healing.
  
  
  CONCLUSIONS
  The use of ASCs may offer a promising solution to treat extended wounds. Pre-clinical studies are however necessary to validate the best skin regeneration technique, which could be used in pediatric surgical translational research.
authors.affiliation: Pediatric Surgery Unit, Fondazione IRCCS Policlinico San Matteo and University of Pavia, 27100, Pavia, Italy. g.pelizzo@smatteo.pv.it.
authors.forename: Gloria
authors.initials: G
authors.lastname: Pelizzo
authors.affiliation: Immunology and Transplantation Laboratory/Cell Factory/Pediatric Hematology/Oncology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. ma.avanzini@smatteo.pv.it.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Avanzini
authors.affiliation: Histology and Embryology Unit, Department of Public Health, Experimental Medicine and Forensic, University of Pavia, Pavia, Italy. antonia.icaro@unipv.it.
authors.forename: Antonia
authors.initials: A
authors.lastname: Icaro Cornaglia
authors.affiliation: Pediatric Surgery Unit, Fondazione IRCCS Policlinico San Matteo and University of Pavia, 27100, Pavia, Italy. hostim@hotmail.com.
authors.forename: Monica
authors.initials: M
authors.lastname: Osti
authors.affiliation: Pediatric Surgery Unit, Fondazione IRCCS Policlinico San Matteo and University of Pavia, 27100, Pavia, Italy. p.romano@smatteo.pv.it.
authors.forename: Piero
authors.initials: P
authors.lastname: Romano
authors.affiliation: Pediatric Surgery Unit, Fondazione IRCCS Policlinico San Matteo and University of Pavia, 27100, Pavia, Italy. l.avolio@smatteo.pv.it.
authors.forename: Luigi
authors.initials: L
authors.lastname: Avolio
authors.affiliation: Immunology and Transplantation Laboratory/Cell Factory/Pediatric Hematology/Oncology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. r.maccario@smatteo.pv.it.
authors.forename: Rita
authors.initials: R
authors.lastname: Maccario
authors.affiliation: Laboratory of Cellular Therapies, Department of Medical and Surgical Sciences for Children and Adults, University Hospital of Modena and Reggio, Emilia, Italy. massimo.dominici@unimore.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Dominici
authors.affiliation: Biometry and Clinical Epidemiology Unit, Scientific Direction, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. a.desilvestri@smatteo.pv.it.
authors.forename: Annalisa
authors.initials: A
authors.lastname: De Silvestri
authors.affiliation: Pediatric Surgery Unit, Fondazione IRCCS Policlinico San Matteo and University of Pavia, 27100, Pavia, Italy. erika.andreatta87@gmail.com.
authors.forename: Erika
authors.initials: E
authors.lastname: Andreatta
authors.affiliation: Pediatric Surgery Unit, Fondazione IRCCS Policlinico San Matteo and University of Pavia, 27100, Pavia, Italy. federico.costanzo01@gmail.com.
authors.forename: Federico
authors.initials: F
authors.lastname: Costanzo
authors.affiliation: Immunology and Transplantation Laboratory/Cell Factory/Pediatric Hematology/Oncology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. melissamantelli@tiscali.it.
authors.forename: Melissa
authors.initials: M
authors.lastname: Mantelli
authors.affiliation: Immunology and Transplantation Laboratory/Cell Factory/Pediatric Hematology/Oncology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. daniela.ingo31@libero.it.
authors.forename: Daniela
authors.initials: D
authors.lastname: Ingo
authors.affiliation: Laboratory of Cellular Therapies, Department of Medical and Surgical Sciences for Children and Adults, University Hospital of Modena and Reggio, Emilia, Italy. mariaserena.piccinno@unimore.it.
authors.forename: Serena
authors.initials: S
authors.lastname: Piccinno
authors.affiliation: Pediatric Unit, Fondazione IRCCS Policlinico San Matteo and University of Pavia, Pavia, Italy. v.calcaterra@smatteo.pv.it.
authors.forename: Valeria
authors.initials: V
authors.lastname: Calcaterra
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000279:Administration, Cutaneous; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D002648:Child; D003094:Collagen / Q000378:metabolism; D004848:Epithelium / Q000473:pathology; D005260:Female; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011817:Rabbits; D012038:Regeneration; D012867:Skin / Q000473:pathology*; D013514:Surgical Procedures, Operative; D014945:Wound Healing
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D003094:Collagen