pH regulates hematopoietic stem cell potential via polyamines

Abstract: Upon ex vivo culture, hematopoietic stem cells (HSCs) quickly lose potential and differentiate into progenitors. The identification of culture conditions that maintain the potential of HSCs ex vivo is therefore of high clinical interest. Here, we demonstrate that the potential of murine and human HSCs is maintained when cultivated for 2 days ex vivo at a pH of 6.9, in contrast to cultivation at the commonly used pH of 7.4. When cultivated at a pH of 6.9, HSCs remain smaller, less metabolically active, less proliferative and show enhanced reconstitution ability upon transplantation compared to HSC cultivated at pH 7.4. HSCs kept at pH 6.9 show an attenuated polyamine pathway. Pharmacological inhibition of the polyamine pathway in HSCs cultivated at pH 7.4 with DFMO mimics phenotypes and potential of HSCs cultivated at pH 6.9. Ex vivo exposure to a pH of 6.9 is therefore a positive regulator of HSC function by reducing polyamines. These findings might improve HSC short‐term cultivation protocols for transplantation and gene therapy interventions.

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch

Bibliographic citation
pH regulates hematopoietic stem cell potential via polyamines ; day:21 ; month:03 ; year:2023 ; extent:27
EMBO reports / European Molecular Biology Organization ; (21.03.2023) (gesamt 27)

Creator
Kumar, Sachin
Vassallo, Jeffrey D.
Nattamai, Kalpana J.
Hassan, Aishlin
Karns, Rebekah
Vollmer, Angelika
Soller, Karin
Sakk, Vadim
Saçma, Mehmet
Nemkov, Travis
D'Alessandro, Angelo
Geiger, Hartmut

DOI
10.15252/embr.202255373
URN
urn:nbn:de:101:1-2023032214020633681614
Rights
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Last update
14.08.2025, 10:52 AM CEST

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