Rejuvenation of the reconstitution potential and reversal of myeloid bias of aged <scp>HSCs</scp> upon <scp>pH</scp> treatment
Aged hematopoietic stem cells (HSCs) show reduced reconstitution potential, limiting their use in transplantation settings in the clinic. We demonstrate here that exposure of aged HSCs ex vivo to a pH of 6.9 instead of the commonly used pH of 7.4 results in enhanced HSCs potential that is consistent with rejuvenation, including attenuation of the myeloid bias of aged HSC and restoration of a youthful frequency of epigenetic polarity. Rejuvenation of aged HSCs by pH 6.9 is, at least in part, due to alterations in the polyamine/methionine pathway within pH 6.9 HSCs, and consequently, attenuation of the production of spermidine also attenuated aging of HSCs. Exposure of aged HSCs to pH 6.9, or pharmacological targeting of the polyamine pathway, might thus extend the use of HSCs from aged donors for therapeutic applications.
Authors
- Hartmut Geiger (ORCID: https://orcid.org/0000-0002-5794-5430)
- Jeffrey D. Vassallo (ORCID: https://orcid.org/0000-0002-4090-3779)
- Kalpana Nattamai
- Rebekah Karns (ORCID: https://orcid.org/0000-0002-9720-4039)
- Angelika Vollmer
- Travis G. Nemkov (ORCID: https://orcid.org/0000-0001-8566-7119)
- Angelo D’Alessandro (ORCID: https://orcid.org/0000-0002-2258-6490)
- Aishlin Hassan (ORCID: https://orcid.org/0000-0003-4427-3564)
- Mehmet Saçma (ORCID: https://orcid.org/0000-0003-3450-674X)
- Sachin Kumar (ORCID: https://orcid.org/0000-0002-3835-8935)
Institutions
- Cincinnati Children's Hospital Medical Center (US)
- Central Drug Research Institute (IN)
- Universität Ulm (DE)
- University of Colorado Anschutz Medical Campus (US)
- University of Cincinnati (US)
- University of Colorado Denver (US)
Publication Details
- Journal
- Aging Cell
- Published
- 2024-09-05
- DOI
- https://doi.org/10.1111/acel.14324
- Primary Topic
- Hematopoietic Stem Cell Transplantation
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Deutsche Forschungsgemeinschaft