Dynamic cellular phenotyping defines specific mobilization mechanisms of human hematopoietic stem and progenitor cells induced by SDF1α versus synthetic agents

• Verfasst von: Monzel, Cornelia [VerfasserIn]
• Verfasst von: Becker, Alexandra S. [VerfasserIn]
• Verfasst von: Saffrich, Rainer [VerfasserIn]
• Verfasst von: Wuchter, Patrick [VerfasserIn]
• Verfasst von: Eckstein, Volker [VerfasserIn]
• Verfasst von: Ho, Anthony Dick [VerfasserIn]
• Verfasst von: Tanaka, Motomu [VerfasserIn]
• Titel: Dynamic cellular phenotyping defines specific mobilization mechanisms of human hematopoietic stem and progenitor cells induced by SDF1α versus synthetic agents
• Verf.angabe: Cornelia Monzel, Alexandra S. Becker, Rainer Saffrich, Patrick Wuchter, Volker Eckstein, Anthony D. Ho and Motomu Tanaka
• E-Jahr: 2018
• Jahr: 30 January 2018
• Umfang: 10 S.
• Fussnoten: Gesehen am 17.09.2019
• Titel Quelle: Enthalten in: Scientific reports
• Ort Quelle: [London] : Springer Nature, 2011
• Jahr Quelle: 2018
• Band/Heft Quelle: 8(2018) Artikel-Nummer 1841, 10 Seiten
• ISSN Quelle: 2045-2322
• DOI: doi:10.1038/s41598-018-19557-x
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1677139420

Abstract

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 models for the bone marrow niche, live cell imaging techniques, and novel tools in statistical physics, we have quantified the functionality of two mobilization agents that 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, plerixafor exhibited no detectable interference with adhesion and migration. We also found that the deformation of HSPC induced by SDF1α or plerixafor was 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.