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Home / Equine Research Bank / J Orthop Res / Chondrocytic differentiation of mesenchymal stem cells seque...
Journal of orthopaedic research : official publication of the Orthopaedic Research Society2001; 19(4); 738-749; doi: 10.1016/S0736-0266(00)00054-1

Chondrocytic differentiation of mesenchymal stem cells sequentially exposed to transforming growth factor-beta1 in monolayer and insulin-like growth factor-I in a three-dimensional matrix.

Abstract: This study evaluated chondrogenesis of mesenchymal progenitor stem cells (MSCs) cultured initially under pre-confluent monolayer conditions exposed to transforming growth factor-beta1 (TGF-beta1), and subsequently in three-dimensional cultures containing insulin-like growth factor I (IGF-I). Bone marrow aspirates and chondrocytes were obtained from horses and cultured in monolayer with 0 or 5 ng of TGF-beta 1 per ml of medium for 6 days. TGF-beta 1 treated and untreated cultures were distributed to three-dimensional fibrin disks containing 0 or 100 ng of IGF-I per ml of medium to establish four treatment groups. After 13 days, cultures were assessed by toluidine blue staining, collagen types I and II in situ hybridization and immunohistochemistry, proteoglycan production by [35S]-sulfate incorporation, and disk DNA content by fluorometry. Mesenchymal cells in monolayer cultures treated with TGF-beta1 actively proliferated for the first 4 days, developed cellular rounding, and formed cell clusters. Treated MSC cultures had a two-fold increase in medium proteoglycan content. Pretreatment of MSCs with TGF-beta1 followed by exposure of cells to IGF-I in three-dimensional culture significantly increased the formation of markers of chondrocytic function including disk proteoglycan content and procollagen type II mRNA production. However, proteoglycan and procollagen type II production by MSC's remained lower than parallel chondrocyte cultures. MSC pretreatment with TGF-beta1 without sequential IGF-I was less effective in initiating expression of markers of chondrogenesis. This study indicates that although MSC differentiation was less than complete when compared to mature chondrocytes, chondrogenesis was observed in IGF-I supplemented cultures, particularly when used in concert with TGF-beta1 pretreatment.
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Publication Date: 2001-08-24 PubMed ID: 11518286DOI: 10.1016/S0736-0266(00)00054-1Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research involves a study on the transformation of mesenchymal stem cells (MSCs) into chondrocytes (cartilage producing cells) with two treatments. Firstly, the cells are treated with a protein, transforming growth factor-beta1 (TGF-beta1), in a one-layer setting, and then with insulin-like growth factor I (IGF-I) in a three-dimensional growth environment.

Methodology

  • MSCs were sourced from horses’ bone marrow and chondrocytes. They were cultured in a monolayer with or without an infusion of 5ng of TGF-beta1 per milliliter of medium for six days.
  • The cultures treated and untreated by TGF-beta1 were then moved to set up a three-dimensional fibrin disk, an environment infused with 100ng of IGF-I per ml. The cells were further divided into four treatment groups.
  • After thirteen days of exposure to the two-step treatment, the cultures were assessed through various methods such as toluidine blue staining, collagen types I and II in situ hybridization and immunohistochemistry, proteoglycan production by radioactive sulphur ([35S]-sulphate), and monitoring DNA content in the disk by fluorometry.

Observations and Findings

  • The MSCs treated with TGF-beta1 in the monolayer setup were observed to proliferate for initial four days, showed a change in cell shape, and grouped as clusters.
  • The treatment showed a two-fold increase in proteoglycan content in the medium; proteoglycans are molecules important in building cartilage tissue.
  • The MSCs which were first treated with TGF-beta1 and then exposed to IGF-I in three-dimensional culture demonstrated a significant rise in the production of disk proteoglycan content and procollagen type II mRNA, key markers of chondrocytic activity.
  • However, despite noticeable activity, the chondrogenesis in MSCs was still lower than that in the mature chondrocyte cultures.
  • Surprisingly, solely treating MSCs with TGF-beta1 without a sequential IGF-I treatment was less effective in stimulating chondrogenesis.

Conclusion

  • This research suggests that the two-step treatment of mesenchymal stem cells (MSCs) with TGF-beta1 and IGF-I effectively triggers chondrogenesis, the transformation of MSCs into cartilage-forming chondrocytes.
  • However, the degree of transformation was found to be less comprehensive compared to mature chondrocytes, despite the fact that chondrogenesis was noticeably higher when IGF-I was used after TGF-beta1 treatment.

Cite This Article

APA
Worster AA, Brower-Toland BD, Fortier LA, Bent SJ, Williams J, Nixon AJ. (2001). Chondrocytic differentiation of mesenchymal stem cells sequentially exposed to transforming growth factor-beta1 in monolayer and insulin-like growth factor-I in a three-dimensional matrix. J Orthop Res, 19(4), 738-749. https://doi.org/10.1016/S0736-0266(00)00054-1

Publication

Journal of orthopaedic research : official publication of the Orthopaedic Research Society
ISSN: 0736-0266
NlmUniqueID: 8404726
Country: United States
Language: English
Volume: 19
Issue: 4
Pages: 738-749

Researcher Affiliations

Worster, A A
  • Comparative Orthopaedics Laboratory, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Brower-Toland, B D
    Fortier, L A
      Bent, S J
        Williams, J
          Nixon, A J

            MeSH Terms

            • Animals
            • Cell Culture Techniques / methods
            • Cell Differentiation / drug effects
            • Chondrocytes / chemistry
            • Chondrocytes / cytology
            • Chondrocytes / physiology
            • Collagen / analysis
            • Collagen / genetics
            • Fibrin
            • Gene Expression / drug effects
            • Glycosaminoglycans / analysis
            • Horses
            • Hydroxyproline / analysis
            • Immunohistochemistry
            • In Situ Hybridization
            • Insulin-Like Growth Factor I / pharmacology
            • Mesoderm / cytology
            • RNA, Messenger / analysis
            • Stem Cells / chemistry
            • Stem Cells / cytology
            • Stem Cells / physiology
            • Transforming Growth Factor beta / pharmacology
            • Transforming Growth Factor beta1

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