Continuous stimulation with differentiation factors is necessary to enhance osteogenic differentiation of human mesenchymal stem cells in-vitro

Abstract

Bone defect treatment belongs to the most challenging fields in orthopedic surgery and requires the well-coordinated application of mesenchymal stem cells (MSC) and differentiation factors. MSC isolated from reaming material (RMSC) and iliac crest (BMSC) in combination with bone morphogenetic protein-7 (BMP-7) and insulin-like growth factor-1 (IGF-1) have been used. The short half-life of both factors limit their applications: a burst release of the factor can probably not induce sustainable differentiation. We stimulated MSC in osteogenic differentiation medium with three different concentrations of BMP-7 or IGF-1: Group A was stimulated continuously, group B for 24 h and group C remained without any stimulation. Osteogenic differentiation was measured after seven and 14 days by alizarin red staining and alkaline phosphatase (ALP) activity. Continuous stimulation led to higher levels of osteogenic differentiation than short-term stimulation. This could lead to a reconsideration of established application forms for differentiation factors, aiming to provide a more sustained release.

Keywords:

• Human mesenchymal stem cells (MSC)
• bone morphogenetic protein-7 (BMP-7)
• insulin-like growth factor-1 (IGF-1)
• tissue engineering

Acknowledgments

We thank Birgit Frey for her expertise with alizarin red staining and Raban Heller for supporting statistical analyses.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This study was supported by a grant of Dres. Majic/Majic-Schlez-Stiftung [3541.29]. Dr. Fabian Westhauser is supported by the ‘Physician Scientist Program’-scholarship introduced by the Medical Faculty of the University of Heidelberg.