title: Direct and indirect co-culture of chondrocytes and mesenchymal stem cells for the generation of polymer/extracellular matrix hybrid constructs.
abstract: In this work, the influence of direct cell-cell contact in co-cultures of mesenchymal stem cells (MSCs) and chondrocytes for the improved deposition of cartilage-like extracellular matrix (ECM) within nonwoven fibrous poly(∊-caprolactone) (PCL) scaffolds was examined. To this end, chondrocytes and MSCs were either co-cultured in direct contact by mixing on a single PCL scaffold or produced via indirect co-culture, whereby the two cell types were seeded on separate scaffolds which were then cultured together in the same system either statically or under media perfusion in a bioreactor. In static cultures, the chondrocyte scaffold of an indirectly co-cultured group generated significantly greater amounts of glycosaminoglycan and collagen than the direct co-culture group initially seeded with the same number of chondrocytes. Furthermore, improved ECM production was linked to greater cellular proliferation and distribution throughout the scaffold in static culture. In perfusion cultures, flow had a significant effect on the proliferation of the chondrocytes. The ECM contents within the chondrocyte-containing scaffolds of the indirect co-culture groups either approximated or surpassed the amounts generated within the direct co-culture group. Additionally, within bioreactor culture there were indications that chondrocytes had an influence on the chondrogenesis of MSCs as evidenced by increases in cartilaginous ECM synthetic capacity. This work demonstrates that it is possible to generate PCL/ECM hybrid scaffolds for cartilage regeneration by utilizing the factors secreted by two different cell types, chondrocytes and MSCs, even in the absence of juxtacrine signaling.
authors.affiliation: Rice University, Department of Bioengineering, MS-142, 6100 Main Street, Houston, TX 77005-1892, USA.
authors.forename: Erica J
authors.initials: EJ
authors.lastname: Levorson
authors.affiliation: Rice University, Department of Chemical and Biomolecular Engineering, MS-362, 6100 Main Street, Houston, TX 77005-1827, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Santoro
authors.affiliation: Rice University, Department of Bioengineering, MS-142, 6100 Main Street, Houston, TX 77005-1892, USA.
authors.forename: F Kurtis
authors.initials: FK
authors.lastname: Kasper
authors.affiliation: Rice University, Department of Bioengineering, MS-142, 6100 Main Street, Houston, TX 77005-1892, USA; Rice University, Department of Chemical and Biomolecular Engineering, MS-362, 6100 Main Street, Houston, TX 77005-1827, USA. Electronic address: mikos@rice.edu.
authors.forename: Antonios G
authors.initials: AG
authors.lastname: Mikos
mesh_terms: D000818:Animals; D019149:Bioreactors; D002417:Cattle; D002452:Cell Count; D019902:Chondrocytes / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D018920:Coculture Techniques / Q000379:methods*; D003094:Collagen / Q000096:biosynthesis; D004247:DNA / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000096:biosynthesis; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D011091:Polyesters / Q000494:pharmacology*; D011817:Rabbits; D013194:Staining and Labeling; D013499:Surface Properties; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D006025:Glycosaminoglycans; D011091:Polyesters; C016240:polycaprolactone; D003094:Collagen; D004247:DNA
keywords: Cartilage tissue engineering; Chondrocyte; Co-culture; Extracellular matrix; Mesenchymal stem cell