TGF-β1, GDF-5, and BMP-2 stimulation induces chondrogenesis in expanded human articular chondrocytes and marrow-derived stromal cells

Meghan K. Murphy, Daniel J. Huey, Jerry C. Hu, Kyriacos A. Athanasiou

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

Replacement of degenerated cartilage with cell-based cartilage products may offer a long-term solution to halt arthritis' degenerative progression. Chondrocytes are frequently used in cell-based FDA-approved cartilage products; yet human marrow-derived stromal cells (hMSCs) show significant translational potential, reducing donor site morbidity and maintaining their undifferentiated phenotype with expansion. This study sought to investigate the effects of transforming growth factor β1 (TGF-β1), growth/differentiation factor 5 (GDF-5), and bone morphogenetic protein 2 (BMP-2) during postexpansion chondrogenesis in human articular chondrocytes (hACs) and to compare chondrogenesis in passaged hACs with that of passaged hMSCs. Through serial expansion, chondrocytes dedifferentiated, decreasing expression of chondrogenic genes while increasing expression of fibroblastic genes. However, following expansion, 10 ng/mL TGF-β1, 100 ng/mL GDF-5, or 100 ng/mL BMP-2 supplementation during three-dimensional aggregate culture each upregulated one or more markers of chondrogenic gene expression in both hACs and hMSCs. Additionally, in both cell types, the combination of TGF-β1, GDF-5, and BMP-2 induced the greatest upregulation of chondrogenic genes, that is, Col2A1, Col2A1/Col1A1 ratio, SOX9, and ACAN, and synthesis of cartilage-specific matrix, that is, glycosaminoglycans (GAGs) and ratio of collagen II/I. Finally, TGF-β1, GDF-5, and BMP-2 stimulation yielded mechanically robust cartilage rich in collagen II and GAGs in both cell types, following 4 weeks maturation. This study illustrates notable success in using the self-assembling method to generate robust, scaffold-free neocartilage constructs using expanded hACs and hMSCs. Stem Cells 2015;33:762-773

Original languageEnglish (US)
Pages (from-to)762-773
Number of pages12
JournalStem Cells
Volume33
Issue number3
DOIs
StatePublished - Mar 1 2015

Fingerprint

Growth Differentiation Factor 5
Chondrogenesis
Bone Morphogenetic Protein 2
Transforming Growth Factors
Stromal Cells
Chondrocytes
Joints
Bone Marrow
Cartilage
Glycosaminoglycans
Gene Expression
Collagen
Osteoarthritis
Up-Regulation
Stem Cells
Morbidity
Phenotype

Keywords

  • Adult stem cells
  • Arthritis
  • Chondrogenesis
  • Differentiation
  • Mesenchymal stem cells
  • Tissue regeneration

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine

Cite this

TGF-β1, GDF-5, and BMP-2 stimulation induces chondrogenesis in expanded human articular chondrocytes and marrow-derived stromal cells. / Murphy, Meghan K.; Huey, Daniel J.; Hu, Jerry C.; Athanasiou, Kyriacos A.

In: Stem Cells, Vol. 33, No. 3, 01.03.2015, p. 762-773.

Research output: Contribution to journalArticle

Murphy, Meghan K. ; Huey, Daniel J. ; Hu, Jerry C. ; Athanasiou, Kyriacos A. / TGF-β1, GDF-5, and BMP-2 stimulation induces chondrogenesis in expanded human articular chondrocytes and marrow-derived stromal cells. In: Stem Cells. 2015 ; Vol. 33, No. 3. pp. 762-773.
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