Abstract
A combination of stem cell therapy and tissue engineering is emerging as one of the most promising approaches for skeletal tissue repair and regeneration. Osteoinduction of human bone marrow mesenchymal stem cells (MSCs) is initiated through local signals or growth factors, of which the bone morphogenetic proteins (BMPs) are the best characterised. Cytomodulin-1 (CM-1), a synthetic heptapeptide with functional similarity to members of the TGF-B super family, has been classified as a novel growth factor associated with osteoinduction of MSCs. However, the effects of CM-1 on human bone MSCs are still unclear. The aim of this study was to determine any effects for CM-1 and its scrambled control (CM-1 SCRAM) on the proliferation and differentiation of human bone marrow MSCs along the osteogenic lineage.
Primary human bone marrow MSCs were cultured in the presence of CM-1 and CM-1 SCRAM at a range of concentrations (10-8M – 10-6M) in vitro for up to three weeks. 100 ng/mL of recombinant human BMP-2 (rhBMP-2) was used as a positive control. At the end of the culture period, histological and biochemical assays were carried out on the cultures.
Biochemical assays revealed that 10-7M of CM-1 significantly stimulated alkaline phosphatase specific activity compared with the negative control group (P< 0.05) in a similar way to the rhBMP-2 positive control group. These data were supported by an observed increase in positive alkaline phosphatase staining in the 10-7M of CM-1 and rhBMP-2 treated cells. However, total DNA content was not significantly different between any of the groups.
This study indicated the potential of using CM-1 as an osteogenic growth factor for skeletal tissue regeneration which may provide an alternative approach to meet the major clinical need in orthopaedics and craniofacial surgery.
* Cytomodulin-1 and the scrambled control were genuine gifts from Professor (emeritus) Rajendra S. Bhatnagar at the Department of Bioengineering, University California Berkley, USA.
Correspondence should be addressed to Mr Carlos Wigderowitz, Senior Lecturer, University Department of Orthopaedic and Trauma Surgery, Ninewells Hospital and Medical School, Dundee DD1 9SY.
