title: Endothelium trans differentiated from Wharton's jelly mesenchymal cells promote tissue regeneration: potential role of soluble pro-angiogenic factors.
abstract: BACKGROUND
  Mesenchymal stem cells have a high capacity for trans-differentiation toward many adult cell types, including endothelial cells. Feto-placental tissue, such as Wharton's jelly is a potential source of mesenchymal stem cells with low immunogenic capacity; make them an excellent source of progenitor cells with a potential use for tissue repair. We evaluated whether administration of endothelial cells derived from mesenchymal stem cells isolated from Wharton's jelly (hWMSCs) can accelerate tissue repair in vivo.
  
  
  METHODS
  Mesenchymal stem cells were isolated from human Wharton's jelly by digestion with collagenase type I. Endothelial trans-differentiation was induced for 14 (hWMSC-End14d) and 30 (hWMSC-End30d) days. Cell phenotyping was performed using mesenchymal (CD90, CD73, CD105) and endothelial (Tie-2, KDR, eNOS, ICAM-1) markers. Endothelial trans-differentiation was demonstrated by the expression of endothelial markers and their ability to synthesize nitric oxide (NO).
  
  
  RESULTS
  hWMSCs can be differentiated into adipocytes, osteocytes, chondrocytes and endothelial cells. Moreover, these cells show high expression of CD73, CD90 and CD105 but low expression of endothelial markers prior to differentiation. hWMSCs-End express high levels of endothelial markers at 14 and 30 days of culture, and also they can synthesize NO. Injection of hWMSC-End30d in a mouse model of skin injury significantly accelerated wound healing compared with animals injected with undifferentiated hWMSC or injected with vehicle alone. These effects were also observed in animals that received conditioned media from hWMSC-End30d cultures.
  
  
  CONCLUSIONS
  These results demonstrate that mesenchymal stem cells isolated from Wharton's jelly can be cultured in vitro and trans-differentiated into endothelial cells. Differentiated hWMSC-End may promote neovascularization and tissue repair in vivo through the secretion of soluble pro-angiogenic factors.
authors.affiliation: Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepción, Concepción, Chile.
authors.forename: Valeria
authors.initials: V
authors.lastname: Aguilera
authors.affiliation: Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepción, Concepción, Chile.
authors.forename: Luis
authors.initials: L
authors.lastname: Briceño
authors.affiliation: Faculty of Medicina, Universidad Católica de la Santísima Concepción, Concepción, Chile.
authors.forename: Hector
authors.initials: H
authors.lastname: Contreras
authors.affiliation: Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepción, Concepción, Chile.
authors.forename: Liliana
authors.initials: L
authors.lastname: Lamperti
authors.affiliation: Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepción, Concepción, Chile.
authors.forename: Esperanza
authors.initials: E
authors.lastname: Sepúlveda
authors.affiliation: Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepción, Concepción, Chile.
authors.forename: Francisca
authors.initials: F
authors.lastname: Díaz-Perez
authors.affiliation: Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepción, Concepción, Chile.
authors.forename: Marcelo
authors.initials: M
authors.lastname: León
authors.affiliation: Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepción, Concepción, Chile.
authors.forename: Carlos
authors.initials: C
authors.lastname: Veas
authors.affiliation: Department of Physiopathology, Faculty of Biological Sciences, University of Concepción, Concepción, Chile.
authors.forename: Rafael
authors.initials: R
authors.lastname: Maura
authors.affiliation: Department of Physiopathology, Faculty of Biological Sciences, University of Concepción, Concepción, Chile.
authors.forename: Jorge Roberto
authors.initials: JR
authors.lastname: Toledo
authors.affiliation: Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepción, Concepción, Chile; Facultad Ciencias de la Salud, Escuela de Tecnología Médica, Universidad San Sebastián, Concepción, Chile.
authors.forename: Paulina
authors.initials: P
authors.lastname: Fernández
authors.affiliation: Facultad Ciencias de la Salud, Escuela de Tecnología Médica, Universidad San Sebastián, Concepción, Chile.
authors.forename: Ambart
authors.initials: A
authors.lastname: Covarrubias
authors.affiliation: Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepción, Concepción, Chile.
authors.forename: Felipe Andrés
authors.initials: FA
authors.lastname: Zuñiga
authors.affiliation: Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepción, Concepción, Chile.
authors.forename: Claudia
authors.initials: C
authors.lastname: Radojkovic
authors.affiliation: Vascular Physiology Laboratory, Group of Investigation in Tumor Angiogenesis (GIANT), Department of Basic Sciences, University of Bío-Bío, Chillán, Chile; Group of Research and Innovation in Vascular Health (GRIVAS Health), Department of Basic Sciences, University of Bío-Bío, Chillán, Chile.
authors.forename: Carlos
authors.initials: C
authors.lastname: Escudero
authors.affiliation: Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepción, Concepción, Chile; Group of Research and Innovation in Vascular Health (GRIVAS Health), Department of Basic Sciences, University of Bío-Bío, Chillán, Chile.
authors.forename: Claudio
authors.initials: C
authors.lastname: Aguayo
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004727:Endothelium / Q000166:cytology / Q000502:physiology*; D005260:Female; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D012867:Skin / Q000293:injuries*; D014945:Wound Healing / Q000502:physiology*
chemical_list: D009569:Nitric Oxide