Cell motility and migration as determinants of stem cell efficacy

Abstract

Background Stem cells` (SC) functional heterogeneity and its poorly understood aetiology impedes clinical development of cell-based therapies in regenerative medicine and oncology. Recent studies suggest a strong correlation between the SC migration potential and their therapeutic efficacy in humans. Designating SC migration as a denominator of functional SC heterogeneity, we sought to identify highly migrating subpopulations within different SC classes and evaluate their therapeutic properties in comparison to the parental non-selected cells. Methods We selected highly migrating subpopulations from mesenchymal and neural SC (sMSC and sNSC), characterized their features including but not limited to migratory potential, trophic factor release and transcriptomic signature. To assess lesion-targeted migration and therapeutic properties of isolated subpopulations in vivo, surgical transplantation and intranasal administration of MSCs in mouse models of glioblastoma and Alzheimer's disease respectively were performed. Findings Comparison of parental non-selected cells with isolated subpopulations revealed superior motility and migratory potential of sMSC and sNSC in vitro. We identified podoplanin as a major regulator of migratory features of sMSC/sNSC. Podoplanin engineering improved oncovirolytic activity of virus-loaded NSC on distantly located glioblastoma cells. Finally, sMSC displayed more targeted migration to the tumour site in a mouse glioblastoma model and remarkably higher potency to reduce pathological hallmarks and memory deficits in transgenic Alzheimer's disease mice. Interpretation Functional heterogeneity of SC is associated with their motility and migration potential which can serve as predictors of SC therapeutic efficacy. Funding This work was supported in part by the Robert Bosch Stiftung (Stuttgart, Germany) and by the IZEPHA grant.

Advances in intranasal application of stem cells in the treatment of central nervous system diseases

“…However, definitively demonstrating which type of intranasally delivered stem cells perform best in reaching appropriate targets and have the best restorative or therapeutic effect may be difficult. We agree with the conclusion of Danielyan et al that the motility and migratory potential of stem cells can serve as predictors of their therapeutic efficacy because they all relate to the functional heterogeneity of stem cells [ 40 ].…”

Losartan Improves Memory, Neurogenesis and Cell Motility in Transgenic Alzheimer’s Mice

“…However, whether a general enhancement of astroglial motility will lead to more effective targeting of Aβ plaques in vivo remains a matter for future investigations. Previous studies have demonstrated the improvement of Aβ plaques and soluble fragments’ clearance from the brains of 3xTg-AD and APP/PS1 mice treated with mesenchymal stem cells (MSC) by simply enhancing the migratory properties of MSC via the selection of highly migratory subpopulations for cell transplantation [ 47 ]. ARBs as potential enhancers of cell migration may be tested for their influence on the migratory properties of different cell therapeutics (adult stem cells, induced pluripotent stem cells, etc.)…”

More Human BM-MSC With Similar Subpopulation Composition and Functional Characteristics Can Be Produced With a GMP-Compatible Fabric Filter System Compared to Density Gradient Technique

“…Surface proteins such as CD271, CD146, MSCA-1, CD106, CD119, CD140a, or distinct mRNA signatures, defining cell clusters within MSC preparations, could be assigned to MSC functions such as differentiation, tissue regeneration, immunomodulation, or wound healing ( Jones and Schäfer, 2015 ; Wu et al, 2016 ; Khong et al, 2019 ; Kuci et al, 2019 ). Moreover, MSC subpopulations’ motility and adhesion capacities can affect their therapeutic efficacy ( Danielyan et al, 2020 ; Schäfer et al, 2020 ).…”

“…The reasons for these observations have not been elucidated completely, but the considerable heterogeneity of MSC preparations may be a relevant contributor. The composition of MSC preparations varies between donors ( Siegel et al, 2013 ), and there is emerging evidence linking MSC subpopulation phenotypes to their therapeutic potential ( Rennert et al, 2016 ; Khong et al, 2019 ; Kuci et al, 2019 ; Danielyan et al, 2020 ).…”