title: Chondrogenic induction of mesenchymal stromal/stem cells from Wharton's jelly embedded in alginate hydrogel and without added growth factor: an alternative stem cell source for cartilage tissue engineering.
abstract: BACKGROUND
  Due to their intrinsic properties, stem cells are promising tools for new developments in tissue engineering and particularly for cartilage tissue regeneration. Although mesenchymal stromal/stem cells from bone marrow (BM-MSC) have long been the most used stem cell source in cartilage tissue engineering, they have certain limits. Thanks to their properties such as low immunogenicity and particularly chondrogenic differentiation potential, mesenchymal stromal/stem cells from Wharton's jelly (WJ-MSC) promise to be an interesting source of MSC for cartilage tissue engineering.
  
  
  METHODS
  In this study, we propose to evaluate chondrogenic potential of WJ-MSC embedded in alginate/hyaluronic acid hydrogel over 28 days. Hydrogels were constructed by the original spraying method. Our main objective was to evaluate chondrogenic differentiation of WJ-MSC on three-dimensional scaffolds, without adding growth factors, at transcript and protein levels. We compared the results to those obtained from standard BM-MSC.
  
  
  RESULTS
  After 3 days of culture, WJ-MSC seemed to be adapted to their new three-dimensional environment without any detectable damage. From day 14 and up to 28 days, the proportion of WJ-MSC CD73(+), CD90(+), CD105(+) and CD166(+) decreased significantly compared to monolayer marker expression. Moreover, WJ-MSC and BM-MSC showed different phenotype profiles. After 28 days of scaffold culture, our results showed strong upregulation of cartilage-specific transcript expression. WJ-MSC exhibited greater type II collagen synthesis than BM-MSC at both transcript and protein levels. Furthermore, our work highlighted a relevant result showing that WJ-MSC expressed Runx2 and type X collagen at lower levels than BM-MSC.
  
  
  CONCLUSIONS
  Once seeded in the hydrogel scaffold, WJ-MSC and BM-MSC have different profiles of chondrogenic differentiation at both the phenotypic level and matrix synthesis. After 4 weeks, WJ-MSC, embedded in a three-dimensional environment, were able to adapt to their environment and express specific cartilage-related genes and matrix proteins. Today, WJ-MSC represent a real alternative source of stem cells for cartilage tissue engineering.
authors.affiliation: UMR 7365 CNRS-Université de Lorraine, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Biopôle, 54505, Vandœuvre-lès-Nancy, France. loic.reppel@univ-lorraine.fr.|CHU de Nancy, Unité de Thérapie Cellulaire et Tissulaire, 54500, Vandœuvre-lès-Nancy, France. loic.reppel@univ-lorraine.fr.|Université de Lorraine, 54000, Nancy, France. loic.reppel@univ-lorraine.fr.|Fédération de Recherche 3209, Bioingénierie Moléculaire Cellulaire et Thérapeutique, 54500, Vandœuvre-lès-Nancy, France. loic.reppel@univ-lorraine.fr.
authors.forename: Loïc
authors.initials: L
authors.lastname: Reppel
authors.affiliation: UMR 7365 CNRS-Université de Lorraine, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Biopôle, 54505, Vandœuvre-lès-Nancy, France. jessica.schiavi.t@gmail.com.|Université de Lorraine, 54000, Nancy, France. jessica.schiavi.t@gmail.com.|Fédération de Recherche 3209, Bioingénierie Moléculaire Cellulaire et Thérapeutique, 54500, Vandœuvre-lès-Nancy, France. jessica.schiavi.t@gmail.com.
authors.forename: Jessica
authors.initials: J
authors.lastname: Schiavi
authors.affiliation: UMR 7365 CNRS-Université de Lorraine, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Biopôle, 54505, Vandœuvre-lès-Nancy, France. naceur.charif@univ-lorraine.fr.|Université de Lorraine, 54000, Nancy, France. naceur.charif@univ-lorraine.fr.|Fédération de Recherche 3209, Bioingénierie Moléculaire Cellulaire et Thérapeutique, 54500, Vandœuvre-lès-Nancy, France. naceur.charif@univ-lorraine.fr.
authors.forename: Naceur
authors.initials: N
authors.lastname: Charif
authors.affiliation: UMR 7365 CNRS-Université de Lorraine, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Biopôle, 54505, Vandœuvre-lès-Nancy, France. leonore.leger@gmail.com.|Université de Lorraine, 54000, Nancy, France. leonore.leger@gmail.com.|Fédération de Recherche 3209, Bioingénierie Moléculaire Cellulaire et Thérapeutique, 54500, Vandœuvre-lès-Nancy, France. leonore.leger@gmail.com.
authors.forename: Léonore
authors.initials: L
authors.lastname: Leger
authors.affiliation: UMR 7365 CNRS-Université de Lorraine, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Biopôle, 54505, Vandœuvre-lès-Nancy, France. Yuhao-wuhan@hotmail.com.|Université de Lorraine, 54000, Nancy, France. Yuhao-wuhan@hotmail.com.|Fédération de Recherche 3209, Bioingénierie Moléculaire Cellulaire et Thérapeutique, 54500, Vandœuvre-lès-Nancy, France. Yuhao-wuhan@hotmail.com.
authors.forename: Hao
authors.initials: H
authors.lastname: Yu
authors.affiliation: UMR 7365 CNRS-Université de Lorraine, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Biopôle, 54505, Vandœuvre-lès-Nancy, France. astrid.pinzano@univ-lorraine.fr.|Fédération de Recherche 3209, Bioingénierie Moléculaire Cellulaire et Thérapeutique, 54500, Vandœuvre-lès-Nancy, France. astrid.pinzano@univ-lorraine.fr.
authors.forename: Astrid
authors.initials: A
authors.lastname: Pinzano
authors.affiliation: UMR 7365 CNRS-Université de Lorraine, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Biopôle, 54505, Vandœuvre-lès-Nancy, France. christel.henrionnet@univ-lorraine.fr.|Fédération de Recherche 3209, Bioingénierie Moléculaire Cellulaire et Thérapeutique, 54500, Vandœuvre-lès-Nancy, France. christel.henrionnet@univ-lorraine.fr.
authors.forename: Christel
authors.initials: C
authors.lastname: Henrionnet
authors.affiliation: UMR 7365 CNRS-Université de Lorraine, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Biopôle, 54505, Vandœuvre-lès-Nancy, France. jf.stoltz@chu-nancy.fr.|CHU de Nancy, Unité de Thérapie Cellulaire et Tissulaire, 54500, Vandœuvre-lès-Nancy, France. jf.stoltz@chu-nancy.fr.|Université de Lorraine, 54000, Nancy, France. jf.stoltz@chu-nancy.fr.|Fédération de Recherche 3209, Bioingénierie Moléculaire Cellulaire et Thérapeutique, 54500, Vandœuvre-lès-Nancy, France. jf.stoltz@chu-nancy.fr.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Stoltz
authors.affiliation: UMR 7365 CNRS-Université de Lorraine, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Biopôle, 54505, Vandœuvre-lès-Nancy, France. d.bensoussan@chu-nancy.fr.|CHU de Nancy, Unité de Thérapie Cellulaire et Tissulaire, 54500, Vandœuvre-lès-Nancy, France. d.bensoussan@chu-nancy.fr.|Université de Lorraine, 54000, Nancy, France. d.bensoussan@chu-nancy.fr.|Fédération de Recherche 3209, Bioingénierie Moléculaire Cellulaire et Thérapeutique, 54500, Vandœuvre-lès-Nancy, France. d.bensoussan@chu-nancy.fr.
authors.forename: Danièle
authors.initials: D
authors.lastname: Bensoussan
authors.affiliation: UMR 7365 CNRS-Université de Lorraine, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Biopôle, 54505, Vandœuvre-lès-Nancy, France. celine.huselstein@univ-lorraine.fr.|Université de Lorraine, 54000, Nancy, France. celine.huselstein@univ-lorraine.fr.|Fédération de Recherche 3209, Bioingénierie Moléculaire Cellulaire et Thérapeutique, 54500, Vandœuvre-lès-Nancy, France. celine.huselstein@univ-lorraine.fr.
authors.forename: Céline
authors.initials: C
authors.lastname: Huselstein
mesh_terms: D000328:Adult; D000464:Alginates / Q000737:chemistry; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002356:Cartilage / Q000502:physiology; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D020219:Chondrogenesis; D024043:Collagen Type II / Q000378:metabolism; D024121:Collagen Type X / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D008875:Middle Aged; D010641:Phenotype; D012038:Regeneration; D023822:Tissue Engineering; D059631:Wharton Jelly / Q000166:cytology / Q000378:metabolism
chemical_list: D000464:Alginates; D024043:Collagen Type II; D024121:Collagen Type X; D050659:Core Binding Factor Alpha 1 Subunit; D006603:Hexuronic Acids; D020100:Hydrogels; D020723:Glucuronic Acid