Abstract

Objective. Osteoarthritis is characterized by an imbalance in cartilage homeostasis, which could potentially be corrected by mesenchymal stem cell (MSC)-based therapies. However, in vivo implantation of undifferentiated MSCs has led to unexpected results. This study was undertaken to establish a model for preconditioning of MSCs toward chondrogenesis as a more effective clinical tool for cartilage regeneration. Methods. A coculture preconditioning system was used to improve the chondrogenic potential of human MSCs and to study the detailed stages of chondrogenesis of MSCs, using a human MSC line, Kp-hMSC, in commitment cocultures with a human chondrocyte line, hPi (labeled with green fluorescent protein [GFP]). In addition, committed MSCs were seeded into a collagen scaffold and analyzed for their neocartilage-forming ability. Results. Coculture of hPi-GFP chondrocytes with Kp-hMSCs induced chondrogenesis, as indicated by the increased expression of chondrogenic genes and accumulation of chondrogenic matrix, but with no effect on osteogenic markers. The chondrogenic process of committed MSCs was initiated with highly activated chondrogenic adhesion molecules and stimulated cartilage developmental growth factors, including members of the transforming growth factor β superfamily and their downstream regulators, the Smads, as well as endothelial growth factor, fibroblast growth factor, insulin-like growth factor, and vascular endothelial growth factor. Furthermore, committed Kp-hMSCs acquired neocartilage-forming potential within the collagen scaffold. Conclusion. These findings help define the molecular markers of chondrogenesis and more accurately delineate the stages of chondrogenesis during chondrocytic differentiation of human MSCs. The results indicate that human MSCs committed to the chondroprogenitor stage of chondrocytic differentiation undergo detailed chondrogenic changes. This model of in vitro chondrogenesis of human MSCs represents an advance in cell-based transplantation for future clinical use.

Original languageEnglish
Pages (from-to)450-459
Number of pages10
JournalArthritis and Rheumatism
Volume60
Issue number2
DOIs
Publication statusPublished - Feb 2009

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Chondrogenesis
Chondrocytes
Mesenchymal Stromal Cells
Coculture Techniques
Cartilage
Green Fluorescent Proteins
Collagen
Endothelial Growth Factors
Fibroblast Growth Factors
Cell Transplantation
Transforming Growth Factors
Somatomedins
Cell- and Tissue-Based Therapy
Osteoarthritis
Vascular Endothelial Growth Factor A
In Vitro Techniques
Regeneration
Intercellular Signaling Peptides and Proteins
Homeostasis
Gene Expression

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology
  • Pharmacology (medical)

Cite this

In vitro stage-specific chondrogenesis of mesenchymal stem cells committed to chondrocytes. / Chen, Wei Hong; Lai, Ming Tang; Wu, Alexander T H; Wu, Chia Che; Gelovani, Juri G.; Lin, Che Tong; Hung, Shih Chieh; Chiu, Wen Ta; Deng, Win Ping.

In: Arthritis and Rheumatism, Vol. 60, No. 2, 02.2009, p. 450-459.

Research output: Contribution to journalArticle

Chen, Wei Hong ; Lai, Ming Tang ; Wu, Alexander T H ; Wu, Chia Che ; Gelovani, Juri G. ; Lin, Che Tong ; Hung, Shih Chieh ; Chiu, Wen Ta ; Deng, Win Ping. / In vitro stage-specific chondrogenesis of mesenchymal stem cells committed to chondrocytes. In: Arthritis and Rheumatism. 2009 ; Vol. 60, No. 2. pp. 450-459.
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abstract = "Objective. Osteoarthritis is characterized by an imbalance in cartilage homeostasis, which could potentially be corrected by mesenchymal stem cell (MSC)-based therapies. However, in vivo implantation of undifferentiated MSCs has led to unexpected results. This study was undertaken to establish a model for preconditioning of MSCs toward chondrogenesis as a more effective clinical tool for cartilage regeneration. Methods. A coculture preconditioning system was used to improve the chondrogenic potential of human MSCs and to study the detailed stages of chondrogenesis of MSCs, using a human MSC line, Kp-hMSC, in commitment cocultures with a human chondrocyte line, hPi (labeled with green fluorescent protein [GFP]). In addition, committed MSCs were seeded into a collagen scaffold and analyzed for their neocartilage-forming ability. Results. Coculture of hPi-GFP chondrocytes with Kp-hMSCs induced chondrogenesis, as indicated by the increased expression of chondrogenic genes and accumulation of chondrogenic matrix, but with no effect on osteogenic markers. The chondrogenic process of committed MSCs was initiated with highly activated chondrogenic adhesion molecules and stimulated cartilage developmental growth factors, including members of the transforming growth factor β superfamily and their downstream regulators, the Smads, as well as endothelial growth factor, fibroblast growth factor, insulin-like growth factor, and vascular endothelial growth factor. Furthermore, committed Kp-hMSCs acquired neocartilage-forming potential within the collagen scaffold. Conclusion. These findings help define the molecular markers of chondrogenesis and more accurately delineate the stages of chondrogenesis during chondrocytic differentiation of human MSCs. The results indicate that human MSCs committed to the chondroprogenitor stage of chondrocytic differentiation undergo detailed chondrogenic changes. This model of in vitro chondrogenesis of human MSCs represents an advance in cell-based transplantation for future clinical use.",
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AU - Lin, Che Tong

AU - Hung, Shih Chieh

AU - Chiu, Wen Ta

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