Despite the first clinical studies reporting on a correlation between
the migration potential of transplanted stem cells and their therapeutic efficacy, it is unclear if effective stem cell therapies require
reliable and sufficient delivery of the cells to the desired anatomic
locations, as well as survival of the cellular graft.

Moreover, the many complex processes involved in stem cell interactions withthe vasculature, the crucial gatekeeper of their entry into the hosts
system, have not been elucidated. Specifically, the majority of systemically applied stem cells accumulate as a first pass effect in parenchymal organs such as the liver, spleen and lung increasing the risk of side effects.

The mechanisms of this phenomenon are not understood, and it is unclear if and how the re-direction of the transplanted stem cells towards the lesioned tissue would impact the efficacy of a stem cell therapy.

In this study, by functionally blocking stem cells adhesion receptors with the cationic linear polymer polyethylenimine, their adhesion capacity to endothelial cells in vitro were decreased and found unexpected differences of chemokine deposits in diseased and healthy rats in the lung vasculature compared to their brains.

Together with the reduced endothelial adhesion in the lung, a simultaneous increase of CCR4 expression resulted in chemokine mediated stem cell homing to lesioned brain tissue and increased migration towards glioblastoma, as well as improved stem cells efficacy in a stroke model.

The paper shows that low adhesion to endothelium in healthy tissue and migration to the lesion site are relevant mechanisms for stem cell therapiesefficacy. Authors’ data identify tissue- and organ-specific regulation of stem cell adhesion to and migration through the vasculature, which, together with the local disease specific microenvironment, impact their targeted migration and therapeutic efficacy.

These findings highlight that the reliable and sufficient delivery of
a cell therapeutic is critical for its efficacy. The novel concept of
modulating adhesion receptor function and chemokine receptor expression by the cationic linear polymer polyethylenimine reported here has the potential to allow highly efficient stem cells homing, hereby contributing to the utilization of their full therapeutic capacity.

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