title: Human CD133(+) bone marrow-derived stem cells promote endometrial proliferation in a murine model of Asherman syndrome.
abstract: OBJECTIVE
  To investigate the engraftment and proliferation of superparamagnetic iron oxide nanoparticles (SPIOs)-labeled human CD133(+) bone marrow-derived stem cells (BMDSCs) in an animal model of Asherman syndrome (AS).
  
  
  METHODS
  Prospective experimental animal study.
  
  
  METHODS
  University research laboratories.
  
  
  METHODS
  Nonobese diabetic mice (strain code 394; NOD.CB17- Prkdc(scid)/NcrCrl) in which AS was induced according to a published protocol.
  
  
  METHODS
  Human CD133(+) BMDSCs were obtained from patients undergoing autologous cell therapy in refractory AS and endometrial atrophy, labeled with SPIOs and injected either intrauterinely (n = 5) or systemically through the tail vein (n = 5) in the animal model.
  
  
  METHODS
  Accumulation of collagen and glycosaminoglycan deposits detected by trichrome staining. Percentage and localization of engrafted human SPIOs-labeled CD133(+) BMDSCs by Prussian blue staining. Cell proliferation assay using Ki67 and reverse transcriptase-polymerase chain reaction (PCR) for specific paracrine factors.
  
  
  RESULTS
  The induction of the AS in the murine model was demonstrated by the accumulation of collagen and glycosaminoglycan deposits in the damaged horns by trichrome staining. Human SPIOs labeled CD133(+) BMDSCs homing represents 0.59% and 0.65% of total number of cells present in the horns after intrauterine or tail vein injections, respectively. Engrafted cells were localized around endometrial blood vessels, inducing proliferation in surrounding cells based on Ki67 and regulation of the paracrine factors thrombospondin 1 and insulin-like growth factor 1.
  
  
  CONCLUSIONS
  The injection of human SPIOs labeled CD133(+) BMDSCs in a murine model of AS confirms that these cells engraft around endometrial vessels, inducing proliferation of surrounding cells through paracrine molecules such as thrombospondin 1 and insulin-like growth factor 1.
  
  
  BACKGROUND
  NCT02144987.
authors.affiliation: Fundación Instituto Valenciano de Infertilidad (FIVI), Department of Obstetrics & Gynecology, School of Medicine, Valencia University and Instituto Universitario IVI/INCLIVA, Valencia, Spain. Electronic address: Irene.Cervello@ivi.es.
authors.forename: Irene
authors.initials: I
authors.lastname: Cervelló
authors.affiliation: Fundación Instituto Valenciano de Infertilidad (FIVI), Department of Obstetrics & Gynecology, School of Medicine, Valencia University and Instituto Universitario IVI/INCLIVA, Valencia, Spain.
authors.forename: Claudia
authors.initials: C
authors.lastname: Gil-Sanchis
authors.affiliation: Instituto Valenciano Infertilidad (IVI) Barcelona, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Santamaría
authors.affiliation: Instituto Valenciano Infertilidad (IVI) Valencia, Valencia, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Cabanillas
authors.affiliation: School of Medicine, Valencia University, Valencia, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Díaz
authors.affiliation: Fundación Instituto Valenciano de Infertilidad (FIVI), Department of Obstetrics & Gynecology, School of Medicine, Valencia University and Instituto Universitario IVI/INCLIVA, Valencia, Spain.
authors.forename: Amparo
authors.initials: A
authors.lastname: Faus
authors.affiliation: Fundación Instituto Valenciano de Infertilidad (FIVI), Department of Obstetrics & Gynecology, School of Medicine, Valencia University and Instituto Universitario IVI/INCLIVA, Valencia, Spain; Instituto Valenciano Infertilidad (IVI) Valencia, Valencia, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pellicer
authors.affiliation: Fundación Instituto Valenciano de Infertilidad (FIVI), Department of Obstetrics & Gynecology, School of Medicine, Valencia University and Instituto Universitario IVI/INCLIVA, Valencia, Spain; School of Medicine, Valencia University, Valencia, Spain; Department of Obstetrics & Gynecology, Stanford University School of Medicine, Stanford University, Stanford, California.
authors.forename: Carlos
authors.initials: C
authors.lastname: Simón
mesh_terms: D000071916:AC133 Antigen; D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001284:Atrophy; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D049109:Cell Proliferation; D002470:Cell Survival; D058948:Cell Tracking / Q000379:methods; D002986:Clinical Trials as Topic; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004717:Endometrium / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism; D006085:Graft Survival; D006175:Gynatresia / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D019899:Paracrine Communication; D010455:Peptides / Q000378:metabolism*; D011446:Prospective Studies; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism*; D019700:Thrombospondin 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D015415:Biomarkers; D006023:Glycoproteins; D006025:Glycosaminoglycans; C583557:IGF1 protein, human; D019394:Ki-67 Antigen; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D019700:Thrombospondin 1; D007334:Insulin-Like Growth Factor I; D003094:Collagen
keywords: Asherman syndrome; CD133(+)cells; bone marrow-derived stem cells (BMDSCs); superparamagnetic iron oxide nanoparticles (SPIOs)