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Abstract
Bone marrow-derived mesenchymal stem cells (MSCs) are adherent cells that differentiate into chondroblasts, osteoblasts and adipocytes. In this short review, we summarize the molecular mechanisms that are known to control osteoblast differentiation and osteogenic potential of MSCs in vitro. We discuss the advances made in gene-based therapy to promote osteogenic differentiation of MSCs and the perspectives for an optimal use of MSCs for bone tissue regeneration or repair. One important challenge at the present time is to identify factors and pathways that promote osteogenic commitment of MSCs in order to use MSCs with functional potential for optimal bone repair in humans. In this context, genomic and proteomic analyses may help to identify molecules that could be used to promote osteogenic differentiation of human MSCs. In the future this may lead to selective therapeutic strategies for tissue engineering application in bone regeneration and repair in humans.
Future perspective
Future research should focus on the development of easy, rapid and reproducible methods to isolate, expand and promote osteogenic differentiation of autologous MSCs for clinical implantation in bone defects in humans. In addition, the use of modern proteomic and genomic platforms to identify factors that could optimally promote the proliferation, commitment and differentiation of hMSCs in vitro and promote their capacity for bone regeneration in vivo, will help move the field forward. The development of gene therapy is another important challenge for the future. Recent studies reported efficient gene delivery in murine or human MSCs Citation[96–100]. Although some efforts have been made to overcome the limitations of vector-mediated gene therapy for bone diseases Citation[87], efficient and safe methods remain to be developed in hMSCs. Finally, it will be useful to develop synthetic biomaterials allowing optimal hMSC adherence and differentiation, in order to increase osteoconductivity for bone tissue engineering. It is expected that the use of hMSCs with biomaterials that deliver safe osteogenic factors may be used in the future as therapeutic tools for bone regeneration in orthopedic therapeutic applications.
Speculative viewpoint on the evolution of the field
Based on existing basic, preclinical or clinical data, it is expected that hMSCs will be used extensively in the future as a source of osteogenic cells for bone tissue engineering. It is likely that the development of cell therapy using MSCs combined with appropriate matrices may have important clinical applications for local bone repair. This leads us to speculate that bone regeneration could be optimally achieved in the future by using appropriate carriers delivering molecules capable of selectively targeting MSCs in order to promote hMSC osteogenic differentiation in a controlled manner. Finally, we can hope that the development of safe and efficient gene therapy in human MSCs may lead to regenerate bone in complex local skeletal disorders.
Acknowledgements
The work of the authors was supported by grants from the Etablissement Français du Sang (2004–08), Inserm PNR Pro-A (France), Genostem (EU) and CNES (France).