Gene expression profiling of human articular cartilage grafts generated by tissue engineering.
Cartilage tissue engineering is applied clinically to cover and regenerate articular cartilage defects. In this study autologous human cartilage tissue engineering grafts based on bioresorbable polyglactin/polydioxanone scaffolds were analyzed on the broad molecular level. RNA from freshly isolated, primary and expanded adult articular chondrocytes and from three-dimensional cartilage grafts were used for gene expression profiling using oligonucleotide microarrays. The capacity of cartilage grafts to form cartilage matrix was evaluated after subcutaneous transplantation into nude mice. Gene expression profiling showed reproducibly the regulation of 905 genes and documented that chondrocytes undergo fundamental changes during cartilage tissue engineering regarding chondrocyte metabolism, growth, and differentiation. Three-dimensional assembly of expanded, dedifferentiated chondrocytes initiated the re-differentiation of cells that was accompanied by the reversal of the expression profile of multiple players of the transforming growth factor (TGF) signaling pathway including growth and differentiation factor-5 and inhibitor of differentiation-1 as well as by the induction of typical cartilage-related matrix genes such as type II collagen and cartilage oligomeric matrix protein. Cartilage grafts formed a cartilaginous matrix after transplantation into nude mice. Three-dimensional tissue culture of expanded articular chondrocytes initiates chondrocyte re-differentiation in vitro and leads to the maturation of cartilage grafts towards hyaline cartilage in vivo.
Kaps
Christian
C
Tissue Engineering Laboratory, Department of Rheumatology, Charité-Universitätsmedizin Berlin, Campus Mitte, Tucholskystr. 2, 10117 Berlin, Germany. christian.kaps@charite.de
Frauenschuh
Simone
S
Endres
Michaela
M
Ringe
Jochen
J
Haisch
Andreas
A
Lauber
Jörg
J
Buer
Jan
J
Krenn
Veit
V
Häupl
Thomas
T
Burmester
Gerd-Rüdiger
GR
Sittinger
Michael
M
D001483:Base Sequence; D002358:Cartilage, Articular / Q000293:injuries / Q000378:metabolism* / Q000637:transplantation*; D002454:Cell Differentiation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D012313:RNA / Q000235:genetics / Q000378:metabolism; D023822:Tissue Engineering / Q000379:methods*
D016326:Extracellular Matrix Proteins; D012313:RNA