Chondrogenesis of adult stem cells from adipose tissue and bone marrow: induction by growth factors and cartilage-derived matrix.
OBJECTIVE
Adipose-derived stem cells (ASCs) and bone marrow-derived mesenchymal stem cells (MSCs) are multipotent adult stem cells with potential for use in cartilage tissue engineering. We hypothesized that these cells show distinct responses to different chondrogenic culture conditions and extracellular matrices, illustrating important differences between cell types.


METHODS
Human ASCs and MSCs were chondrogenically differentiated in alginate beads or a novel scaffold of reconstituted native cartilage-derived matrix with a range of growth factors, including dexamethasone, transforming growth factor beta3, and bone morphogenetic protein 6. Constructs were analyzed for gene expression and matrix synthesis.


RESULTS
Chondrogenic growth factors induced a chondrocytic phenotype in both ASCs and MSCs in alginate beads or cartilage-derived matrix. MSCs demonstrated enhanced type II collagen gene expression and matrix synthesis as well as a greater propensity for the hypertrophic chondrocyte phenotype. ASCs had higher upregulation of aggrecan gene expression in response to bone morphogenetic protein 6 (857-fold), while MSCs responded more favorably to transforming growth factor beta3 (573-fold increase).


CONCLUSIONS
ASCs and MSCs are distinct cell types as illustrated by their unique responses to growth factor-based chondrogenic induction. This chondrogenic induction is affected by the composition of the scaffold and the presence of serum.
Diekman
Brian O
BO
Departments of Surgery and Biomedical Engineering, Duke University Medical Center, Durham, North Carolina 27710, USA.
Rowland
Christopher R
CR
Lennon
Donald P
DP
Caplan
Arnold I
AI
Guilak
Farshid
F
D000273:Adipose Tissue / Q000166:cytology*; D000328:Adult; D053687:Adult Stem Cells / Q000166:cytology* / Q000187:drug effects; D000464:Alginates / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects; D055418:Bone Morphogenetic Protein 6 / Q000494:pharmacology; D002356:Cartilage / Q000378:metabolism*; D020219:Chondrogenesis / Q000187:drug effects*; D004247:DNA / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D020723:Glucuronic Acid / Q000494:pharmacology; D006025:Glycosaminoglycans / Q000378:metabolism; D006603:Hexuronic Acids / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D054457:Tissue Scaffolds / Q000737:chemistry; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D000464:Alginates; D055418:Bone Morphogenetic Protein 6; D016326:Extracellular Matrix Proteins; D006025:Glycosaminoglycans; D006603:Hexuronic Acids; D036341:Intercellular Signaling Peptides and Proteins; D016212:Transforming Growth Factor beta; D020723:Glucuronic Acid; D004247:DNA