Scaffold Free 3D Culture of Mesenchymal Stem Cells; Implications for Regenerative Medicine

Mesenchymal stem cells (MSCs) are recognized as important sources for regenerative medicine (RM). Adherent cultures, long time considered definitory for MSCs phenotype, are relatively easy to perform and to assess. Two dimensional cell expansion systems, however, have been shown to decrease stemness and to induce cellular senescence therefore impeding on MSC therapeutic potential. Multicellular aggregates known as spheroids are a form of three dimensional (3D) culture increasingly recognized to improve MSC differentiation potential to mesenchymal and non-mesenchymal lineages, to increase cytokine and growth factor release as well as cell trafficking and survival after transplantation. Data about improved vasculogenesis and tissue regeneration potential of spheroid cultured MSCs are already available, making this method attractive for regenerative strategies in wound healing, revascularization after myocardial and cerebral infarctation or peripheral ischemia. In-depth genetic and epigenetic profiling of MSCs in this particular state would be needed in order to predict their therapeutic potential for RM. Better understanding of changes in cellular phenotype that occurs in spontaneous 3D and the implication for in vivo cell behavior as well as cell host interaction after transplantation are required before clinical applications.