Effect of stem cells of dental pulp origin on osseointegration of titanium implant in a novel rat vertebra model.

During that last decade a large number of experiments showed the successful application of stem cells in achieving large bone volume regeneration. On the contrary, our knowledge about the promotion of implant osseointegration by stem cell is sporadic. Recently, our research group has carried out an array of studies aiming the characterization of postnatal stem cells of dental origin. In addition, we have developed a novel quantitative model for implant osseointegration in rat tail vertebrae. In the present work we aimed to study how the implant osseointegration process is affected by mesenchymal stem cells of rat dental pulp origin (DPSC) when cells are undifferentiated or predifferentiated into osteogenic direction. Our results show that undifferentiated pulp cells inserted between the implant and the bone slow down the osseointegration process. On the other hand, pre-differentiated DPSCs do not have a similar adverse effect any more. Our data suggest that the success of mesenchymal stem cell application to promote implant osseointegration is highly dependent on the applied conditions, particularly on the parallel applicatioh of scaffolds and osteogenic components.

STRO-1 positive cell expansion during osteogenic differentiation: A comparative study of three mesenchymal stem cell types of dental origin.

OBJECTIVE: Although the osteogenic differentiation potential of mesenchymal stem cells of dental origin is well established, the roles of different marker proteins in this process remain to be clarified. Our aim was to compare the cellular and molecular changes, focusing in particular on mesenchymal stem cell markers, during in vitro osteogenesis in three dental stem cell types: dental follicle stem cells (DFSCs), periodontal ligament stem cells (PDLSCs) and dental pulp stem cells (DPSCs). DESIGN: Human DFSCs, PDLSCs and DPSCs were isolated, cultured and their osteogenic differentiation was induced for 3 weeks. Mineralization was assessed by von Kossa staining and calcium concentration measurements. The expression of mesenchymal and osteogenic markers was studied by immunocytochemistry and qPCR techniques. Alkaline phosphatase (ALP) activity and the frequency of STRO-1 positive cells were also quantified. RESULTS: The three cultures all showed abundant mineralization, with high calcium content by day 21. The expression of vimentin and nestin was sustained after osteogenic induction. The osteogenic medium induced a considerable elevation of STRO-1 positive cells. By day 7, the ALP mRNA level had increased more than 100-fold in DFSCs, PDLSCs, and DPSCs. Quantitative PCR results indicated dissimilarities of osteoblastic marker levels in the three dental stem cell cultures. CONCLUSIONS: DFSCs, PDLSCs and DPSCs have similar functional osteogenic differentiation capacities although their expressional profiles of key osteogenic markers show considerable variations. The STRO-1 positive cell fraction expands during osteogenic differentiation while vimentin and nestin expression remain high. For identification of stemness, functional studies rather than marker expressions are needed.

Novel possible pharmaceutical research tools: stem cells, gene delivery and their combination.

Both stem cell research and gene delivery are very promising fields of today's biomedical research. In the present review we first attempt to summarize the state of the art in stem cell research. We describe the major categories of stem cells based on cell sources: embryonic, fetal, postnatal and induced pluripotent stem cells. We then present new data on stem cell cultures of dental pulp origin as examples of the progress of postnatal stem cell research. Afterwards, we briefly summarize the most promising achievements in the field of gene delivery. As an example of such advances, we describe novel in vitro and in vivo gene delivery studies to demonstrate that salivary glands are highly potential targets for gene therapy: they can be used to produce therapeutic peptides delivered either into the oral cavity or into the systemic circulation. Finally, we describe and compare studies combining the use of stem cells and gene delivery. We conclude that stem cell therapy and gene delivery alone are both very exciting research areas, and they may act in synergy when used in combination.