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Nitric Oxide in the Control of the in vitro Proliferation and Differentiation of Human Hematopoietic Stem and Progenitor Cells

Hümmer, Julia 1; Kraus, Saskia 1; Brändle, Katharina 1; Lee-Thedieck, Cornelia
1 Institut für Funktionelle Grenzflächen (IFG), Karlsruher Institut für Technologie (KIT)

Abstract:
Hematopoietic stem and progenitor cell (HSPC) transplantation is the best-studied cellular therapy and successful in vitro control of HSPCs has wide clinical implications. Nitric oxide (NO) is a central signaling molecule in vivo and has been implicated in HSPC mobilization to the blood stream in mice. The influence of NO on HSPC behavior in vitro is, however, largely obscure due to the variety of employed cell types, NO administration systems, and used concentration ranges in the literature. Additionally, most studies are based on murine cells, which do not necessarily mimic human HSPC behavior. Thus, the aim of the present study was the systematic, concentration-dependent evaluation of NO-mediated effects on human HSPC behavior in vitro. By culture in the presence of the long-term NO donor diethylenetriamine/nitric oxide adduct (DETA/NO) in a nontoxic concentration window, a biphasic role of NO in the regulation of HSPC behavior was identified: Low DETA/NO concentrations activated classical NO signaling, identified via increased intracellular cyclic guanosine monophosphate (cGMP) levels and proteinkinases G (PKG)-dependent vasodilator-stimulated phosphoprotein (VASP) phosphorylation and mediated a pro-proliferative response of HSPCs. ... mehr


Verlagsausgabe §
DOI: 10.5445/IR/1000130513
Veröffentlicht am 19.03.2021
Originalveröffentlichung
DOI: 10.3389/fcell.2020.610369
Scopus
Zitationen: 1
Web of Science
Zitationen: 1
Dimensions
Zitationen: 1
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Funktionelle Grenzflächen (IFG)
Publikationstyp Zeitschriftenaufsatz
Publikationsmonat/-jahr 02.2021
Sprache Englisch
Identifikator ISSN: 2296-634X
KITopen-ID: 1000130513
HGF-Programm 43.33.11 (POF IV, LK 01) Adaptive and Bioinstructive Materials Systems
Erschienen in Frontiers in Cell and Developmental Biology
Verlag Frontiers Media
Band 8
Seiten Art.-Nr.: 610369
Vorab online veröffentlicht am 09.02.2021
Nachgewiesen in Dimensions
Web of Science
Scopus
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