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Priming mesenchymal stem cells to develop “super stem cells”

sarah Jonas

The stem cell pre-treatment approaches at cellular and sub-cellular levels encompass physical manipulation of stem cells to growth factor treatment, genetic manipulation, and chemical and pharmacological treatment, each strategy having advantages and limitations. Most of these pre-treatment protocols are non-combinative. This editorial is a continuum of Li et al’s published article and Wan et al’s editorial focusing on the significance of pre-treatment strategies to enhance their stemness, immunoregulatory, and immunosuppressive properties. They have elaborated on the intricacies of the combinative pre-treatment protocol using pro-inflammatory cytokines and hypoxia. Applying a well-defined multi-pronged combinatorial strategy of mesenchymal stem cells (MSCs), pre-treatment based on the mechanistic understanding is expected to develop “Super MSCs”, which will create a transformative shift in MSC-based therapies in clinical settings, potentially revolutionizing the field. Once optimized, the standardized protocols may be used with slight modifications to pre-treat different stem cells to develop “super stem cells” with augmented stemness, functionality, and reparability for diverse clinical applications with better outcomes.

Key Words: Cell survival, Cell therapy, Preconditioning, Pre-treatment, Stem cells, Super stem cells

Core Tip: Stem cell pre-treatment is a promising approach for accentuating their stemness and reparability and improving their resistance to apoptosis in the harsh microenvironment of the injured tissue. The current stem cell pre-treatment protocols allow for enhancing their therapeutic efficacy to surmount the limitations of mesenchymal stem cells (MSCs), i.e., mobility, survival, engraftment, and paracrine activity. Besides a novel sub-cellular preconditioning strategy, the combinative preconditioning approach exposing the cells to a proinflammatory milieu under hypoxia improves MSCs’ immunoregulatory potential. Refining a combinatorial pre-treatment protocol using a well-defined mechanistic understanding may allow the exploitation of the full benefits of the pre-treated “super MSCs” for enhanced stemness, functionality, and reparability, including immunosuppressive and immunomodulatory properties.