title: Response of human chondrocytes and mesenchymal stromal cells to a decellularized human dermis.
abstract: BACKGROUND
  Although progress has been made in the treatment of articular cartilage lesions, they are still a major challenge because current techniques do not provide satisfactory long-term outcomes. Tissue engineering and the use of functional biomaterials might be an alternative regenerative strategy and fulfill clinical needs. Decellularized extracellular matrices have generated interest as functional biologic scaffolds, but there are few studies on cartilage regeneration. The aim of this study was to evaluate in vitro the biological influence of a newly developed decellularized human dermal extracellular matrix on two human primary cultures.
  
  
  METHODS
  Normal human articular chondrocytes (NHAC-kn) and human mesenchymal stromal cells (hMSC) from healthy donors were seeded in polystyrene wells as controls (CTR), and on decellularized human dermis batches (HDM_derm) for 7 and 14 days. Cellular proliferation and differentiation, and anabolic and catabolic synthetic activity were quantified at each experimental time. Histology and scanning electron microscopy were used to evaluate morphology and ultrastructure.
  
  
  RESULTS
  Both cell cultures had a similar proliferation rate that increased significantly (p < 0.0005) at 14 days. In comparison with CTR, at 14 days NHAC-kn enhanced procollagen type II (CPII, p < 0.05) and aggrecan synthesis (p < 0.0005), whereas hMSC significantly enhanced aggrecan synthesis (p < 0.0005) and transforming growth factor-beta1 release (TGF-β1, p < 0.0005) at both experimental times. Neither inflammatory stimulus nor catabolic activity induction was observed. By comparing data of the two primary cells, NHAC-kn synthesized significantly more CPII than did hMSC at both experimental times (p < 0.005), whereas hMSC synthesized more aggrecan at 7 days (p < 0.005) and TGF-β1 at both experimental times than did NHAC-kn (p < 0.005).
  
  
  CONCLUSIONS
  The results obtained showed that in in vitro conditions HDM_derm behaves as a suitable scaffold for the growth of both well-differentiated chondrocytes and undifferentiated mesenchymal cells, thus ensuring a biocompatible and bioactive substrate. Further studies are mandatory to test the use of HDM_derm with tissue engineering to assess its therapeutic and functional effectiveness in cartilage regeneration.
authors.affiliation: Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopaedic Institute IRCCS, Bologna, Italy. gianluca.giavaresi@ior.it
authors.forename: Gianluca
authors.initials: G
authors.lastname: Giavaresi
authors.forename: Elena
authors.initials: E
authors.lastname: Bondioli
authors.forename: Davide
authors.initials: D
authors.lastname: Melandri
authors.forename: Roberto
authors.initials: R
authors.lastname: Giardino
authors.forename: Matilde
authors.initials: M
authors.lastname: Tschon
authors.forename: Paola
authors.initials: P
authors.lastname: Torricelli
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cenacchi
authors.forename: Roberto
authors.initials: R
authors.lastname: Rotini
authors.forename: Alessandro
authors.initials: A
authors.lastname: Castagna
authors.forename: Francesca
authors.initials: F
authors.lastname: Veronesi
authors.forename: Stefania
authors.initials: S
authors.lastname: Pagani
authors.forename: Milena
authors.initials: M
authors.lastname: Fini
mesh_terms: D053674:Aggrecans / Q000378:metabolism; D001672:Biocompatible Materials; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism* / Q000648:ultrastructure; D020219:Chondrogenesis; D024043:Collagen Type II / Q000378:metabolism; D020405:Dermis / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning; D011347:Procollagen / Q000378:metabolism; D013997:Time Factors; D046509:Tissue Culture Techniques; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D053674:Aggrecans; D001672:Biocompatible Materials; D024043:Collagen Type II; D053583:Interleukin-1beta; D011347:Procollagen; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3