title: Mesenchymal stromal cells from human umbilical cords display poor chondrogenic potential in scaffold-free three dimensional cultures.
abstract: Many researchers world over are currently investigating the suitability of stromal cells harvested from foetal tissues for allogeneic cell transplantation therapies or for tissue engineering purposes. In this study, we have investigated the chondrogenic potential of mesenchymal stromal cells (MSCs) isolated from whole sections of human umbilical cord or mixed cord (UCSCs-MC), and compared them with cells isolated from synovial membrane (SMSCs), Hoffa's fat pad (HFPSCs) and cartilage. All MSCs were positive for surface markers including CD73, CD90, CD105, CD44, CD146 and CD166, but negative for CD11b, CD19, CD34, CD45 and HLA-DR in addition to CD106 and CD271. Chondrogenic potential of all cell sources was studied using 3D pellet cultures incubated in the presence of different combinations of anabolic substances such as dexamethasone, IGF-1, TGF-β1, TGF-β3, BMP-2 and BMP-7. BMP-2 and dexamethasone in combination with TGF-β1 or TGF-β3 excelled at inducing chondrogenesis on SMSCs, HFPSCs and chondrocytes, as measured by glycosaminoglycans and collagen type II staining of pellets, quantitative glycosaminoglycan expression, quantitative PCR of cartilage signature genes and electron microscopy. In contrast, none of the tested growth factor combinations was sufficient to induce chondrogenesis on UCSCs-MC. Moreover, incubation of UCSCs-MC spheroids in the presence of cartilage pieces or synovial cells in co-cultures did not aid chondrogenic induction. In summary, we show that in comparison with MSCs harvested from adult joint tissues, UCSCs-MC display poor chondrogenic abilities. This observation should alert researchers at the time of considering UCSCs-MC as cartilage forming cells in tissue engineering or repair strategies.
authors.affiliation: Institute of Clinical Medicine, University of Tromsø, Tromsø, 9037, Norway.inigo.martinez@uit.no.
authors.forename: A
authors.initials: A
authors.lastname: Islam
authors.forename: A K
authors.initials: AK
authors.lastname: Hansen
authors.forename: C
authors.initials: C
authors.lastname: Mennan
authors.forename: I
authors.initials: I
authors.lastname: Martinez-Zubiaurre
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000648:ultrastructure; D002356:Cartilage / Q000166:cytology; D018929:Cell Culture Techniques / Q000379:methods*; D049109:Cell Proliferation; D002469:Cell Separation; D020219:Chondrogenesis; D018920:Coculture Techniques; D004247:DNA / Q000378:metabolism; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D008875:Middle Aged; D010641:Phenotype; D018874:Spheroids, Cellular / Q000166:cytology / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology; D013583:Synovial Membrane / Q000166:cytology / Q000648:ultrastructure; D054457:Tissue Scaffolds / Q000737:chemistry*; D014470:Umbilical Cord / Q000166:cytology*
chemical_list: D006025:Glycosaminoglycans; D004247:DNA