Dynamic cellular phenotyping defines specific mobilization mechanisms of human hematopoietic stem and progenitor cells induced by SDF1α versus synthetic agents
2018
Efficient mobilization of hematopoietic stem and progenitor cells (HSPC) is one of the most crucial issues for harvesting an adequate amount of peripheral HSPC for successful clinical transplantation. Applying well-defined
surrogate modelsfor the bone marrow niche,
live cell imagingtechniques, and novel tools in
statistical physics, we have quantified the functionality of two
mobilization agentsthat have been applied in the clinic,
NOX-A12 and AMD3100 (
plerixafor), as compared to a naturally occurring chemokine in the bone marrow, SDF1α. We found that
NOX-A12, an L-enantiomeric RNA oligonucleotide to SDF1, significantly reduced the adhesion of HSPC to the niche surface mediated via the
CXCR4-SDF1α axis, and stretched the migration trajectories of the HSPC. We found that the stretching of trajectories by
NOX-A12 was more prominent than that by SDF1α. In contrast,
plerixaforexhibited no detectable interference with adhesion and migration. We also found that the deformation of HSPC induced by SDF1α or
plerixaforwas also drastically suppressed in the presence of
NOX-A12. This novel technology of quantitative assessment of “dynamic phenotypes” by physical tools has therefore enabled us to define different mechanisms of function for various extrinsic factors compared to naturally occurring chemokines.
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