title: Harnessing Wharton's jelly stem cell differentiation into bone-like nodule on calcium phosphate substrate without osteoinductive factors.
abstract: An important aim of bone regenerative medicine is to design biomaterials with controlled chemical and topographical features to guide stem cell fate towards osteoblasts without addition of specific osteogenic factors. Herein, we find that sprayed bioactive and biocompatible calcium phosphate substrates (CaP) with controlled topography induce, in a well-orchestrated manner, Wharton's jelly stem cells (WJ-SCs) differentiation into osteoblastic lineage without any osteogenic supplements. The resulting WJ-SCs commitment exhibits features of native bone, through the formation of three-dimensional bone-like nodule with osteocyte-like cells embedded into a mineralized type I collagen. To our knowledge, these results present the first observation of a whole differentiation process from stem cell to osteocytes-like on a synthetic material. This suggests a great potential of sprayed CaP and WJ-SCs in bone tissue engineering. These unique features may facilitate the transition from bench to bedside and the development of successful engineered bone.
  
  
  
  Designing materials to direct stem cell fate has a relevant impact on stem cell biology and provides insights facilitating their clinical application in regenerative medicine. Inspired by natural bone compositions, a friendly automated spray-assisted system was used to build calcium phosphate substrate (CaP). Sprayed biomimetic solutions using mild conditions led to the formation of CaP with controlled physical properties, good bioactivity and biocompatibility. Herein, we show that via optimization of physical properties, CaP substrate induce osteogenic differentiation of Wharton's jelly stem cells (WJ-SCs) without adding osteogenic supplement factors. These results suggest a great potential of sprayed CaP and WJ-SCs in bone tissue engineering and may facilitate the transition from bench to beside and the development of clinically successful engineered bone.
authors.affiliation: EA 4691, Biomatériaux et Inflammation en Site Osseux (BIOS), SFR-CAP Santé (FED 4231), Université de Reims Champagne Ardenne, Reims, France; UFR d'odontologie, Université de Reims Champagne Ardenne, Reims, France.
authors.forename: S
authors.initials: S
authors.lastname: Mechiche Alami
authors.affiliation: EA 4691, Biomatériaux et Inflammation en Site Osseux (BIOS), SFR-CAP Santé (FED 4231), Université de Reims Champagne Ardenne, Reims, France; UFR d'odontologie, Université de Reims Champagne Ardenne, Reims, France.
authors.forename: H
authors.initials: H
authors.lastname: Rammal
authors.affiliation: Laboratoire d'anatomie et cytologie pathologique, Centre Hospitalo-Universitaire, Hôpital Robert Debré, Reims, France.
authors.forename: C
authors.initials: C
authors.lastname: Boulagnon-Rombi
authors.affiliation: EA 4691, Biomatériaux et Inflammation en Site Osseux (BIOS), SFR-CAP Santé (FED 4231), Université de Reims Champagne Ardenne, Reims, France; UFR d'odontologie, Université de Reims Champagne Ardenne, Reims, France.
authors.forename: F
authors.initials: F
authors.lastname: Velard
authors.affiliation: EA 4695, Laboratoire d'Ingénierie et Sciences des Matériaux (LISM), Université de Reims Czampagne Ardenne, Reims, France.
authors.forename: F
authors.initials: F
authors.lastname: Lazar
authors.affiliation: EA 4695, Laboratoire d'Ingénierie et Sciences des Matériaux (LISM), Université de Reims Czampagne Ardenne, Reims, France.
authors.forename: R
authors.initials: R
authors.lastname: Drevet
authors.affiliation: EA 4691, Biomatériaux et Inflammation en Site Osseux (BIOS), SFR-CAP Santé (FED 4231), Université de Reims Champagne Ardenne, Reims, France; UFR d'odontologie, Université de Reims Champagne Ardenne, Reims, France.
authors.forename: D
authors.initials: D
authors.lastname: Laurent Maquin
authors.affiliation: EA 4691, Biomatériaux et Inflammation en Site Osseux (BIOS), SFR-CAP Santé (FED 4231), Université de Reims Champagne Ardenne, Reims, France; UFR de Pharmacie, Université de Reims Champagne Ardenne, Reims, France.
authors.forename: S C
authors.initials: SC
authors.lastname: Gangloff
authors.affiliation: INSERM, UMR-S 1121, "Biomatériaux et Bioingénierie", Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France.
authors.forename: J
authors.initials: J
authors.lastname: Hemmerlé
authors.affiliation: INSERM, UMR-S 1121, "Biomatériaux et Bioingénierie", Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France.
authors.forename: J C
authors.initials: JC
authors.lastname: Voegel
authors.affiliation: CNRS, UMR 7564, Laboratoire de Chimie Physique et Microbiologie pour l'Environnement (LCPME), Université de Lorraine, Nancy, France.
authors.forename: G
authors.initials: G
authors.lastname: Francius
authors.affiliation: INSERM, UMR-S 1121, "Biomatériaux et Bioingénierie", Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France; Institut Charles Sadron, Centre National de la Recherche Scientifique, Université de Strasbourg, Starsbourg, France; University of Strasbourg Institute of Advanced Study, Strasbourg, France; Institut Universitaire de France, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Schaaf
authors.affiliation: Institut Charles Sadron, Centre National de la Recherche Scientifique, Université de Strasbourg, Starsbourg, France.
authors.forename: F
authors.initials: F
authors.lastname: Boulmedais
authors.affiliation: EA 4691, Biomatériaux et Inflammation en Site Osseux (BIOS), SFR-CAP Santé (FED 4231), Université de Reims Champagne Ardenne, Reims, France; UFR d'odontologie, Université de Reims Champagne Ardenne, Reims, France. Electronic address: halima.kerdjoudj@univ-reims.fr.
authors.forename: H
authors.initials: H
authors.lastname: Kerdjoudj
mesh_terms: D001672:Biocompatible Materials / Q000494:pharmacology; D001842:Bone and Bones / Q000166:cytology*; D002130:Calcium Phosphates / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D018625:Microscopy, Atomic Force; D016348:Osseointegration / Q000187:drug effects*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology* / Q000648:ultrastructure; D013499:Surface Properties; D059631:Wharton Jelly / Q000166:cytology*
chemical_list: D001672:Biocompatible Materials; D002130:Calcium Phosphates; C020243:calcium phosphate
keywords: Bone regeneration; Bone-like nodule; Calcium phosphate; Osteogenic factors free; Wharton’s jelly stem cells