Fibronectin Stimulates Migration and Proliferation, But Not Chondrogenic Differentiation of Human Subchondral Progenitor Cells

Abstract

Aims: To evaluate the impact of human plasma-derived fibronectin (FN) on human subchondral mesenchymal progenitor cells regarding cell migration, proliferation, and chondrogenic differentiation. Materials & methods: Human subchondral mesenchymal progenitor cells were analyzed for their migration capacity upon treatment with human plasma-derived FN. Proliferation activity was evaluated by DNA content. For chondrogenesis, cells were cultured in high-density pellet cultures in the presence of FN, TGFβ3, and a combination thereof. Results: Treatment of progenitors with FN significantly increased the number of migrating cells and elevated proliferative activity. Histological staining indicated formation of an extracellular matrix with type II collagen. Gene expression analysis gave no evidence for chondrogenic differentiation mediated by FN, but revealed a significant induction of type II collagen expression. Conclusion: FN has a potential to recruit human subchondral mesenchymal progenitor cells, possibly supporting proliferation and matrix assembly in cartilage repair procedures using bioactive implants after microfracture treatment.

Keywords::

• cartilage regeneration
• chondrogenesis
• fibronectin
• microfracture
• migration
• proliferation

Author contribution

JP Krüger, S Lau and M Endres, carried out the migration and proliferation assay, as well as gene expression analysis. RH Kalkreuth performed the cell culture studies and histological analysis. PC Kreuz and P Niemeyer contributed to the conception and design of study. C Kaps designed the study, C Kaps and RH Kalkreuth drafted the manuscript. All authors revised the manuscript critically and finally approved it.

Acknowledgements

The authors are very grateful to Samuel Vetterlein for the excellent technical assistance.

Financial & competing interests disclosure

This study was supported by the Bundesministerium für Bildung und Forschung (ZINK II: 13N12597). JP Krüger, M Endres, C Kaps are employees of TransTissue Technologies GmbH (TTT), a subsidiary of BioTissue Technologies GmbH (BTT). TTT develops products and cartilage treatment strategies in the field of regenerative medicine. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This study was supported by the Bundesministerium für Bildung und Forschung (ZINK II: 13N12597). JP Krüger, M Endres, C Kaps are employees of TransTissue Technologies GmbH (TTT), a subsidiary of BioTissue Technologies GmbH (BTT). TTT develops products and cartilage treatment strategies in the field of regenerative medicine. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.