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. 2025 Sep 17;43(10):sxaf047.
doi: 10.1093/stmcls/sxaf047.

15-PGDH inhibition enhances hematopoietic regeneration during aging

Rahul Chaudhary  1   2 , Brittany A Cordova  1   2 , Marcus Hong  1   2 , Bailey R Klein  1   2 , Lyannah A Contreras  1   2 , Ritisha Rashmil  1   2 , Filip Goshevski  1   2 , Julianne N P Smith  1   2 , Derek J Taylor  1   2   3 , Andrew A Pieper  4   5   6   7   8   9 , Sanford Markowitz  1   2   10 , Amar B Desai  1   2
Affiliations

15-PGDH inhibition enhances hematopoietic regeneration during aging

Rahul Chaudhary et al. Stem Cells. .

Abstract

Hematopoietic aging is characterized by diminished stem cell regenerative capacity and an increased risk of hematologic dysfunction. We previously identified that the prostaglandin-degrading enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) regulates hematopoietic stem cell (HSC) activity. Here, we expand on this work and demonstrate that in aged mice: (1) 15-PGDH expression and activity remain conserved in the bone marrow (BM) and spleen, suggesting that it remains a viable therapeutic target in aging; (2) prolonged PGDH inhibition (PGDHi) significantly increases the frequency and number of phenotypic hematopoietic stem and progenitor cells across multiple compartments, with transcriptional changes indicative of enhanced function; (3) PGDHi-treated BM enhances short-term hematopoietic recovery following transplantation, leading to improved peripheral blood output and accelerated multilineage reconstitution; and (4) PGDHi confers a competitive advantage in primary hematopoietic transplantation while mitigating age-associated myeloid bias in secondary transplants. Notably, these effects occur without perturbing steady-state blood production, suggesting that PGDHi enhances hematopoiesis under regenerative conditions while maintaining homeostasis. Our work identifies PGDHi as a translatable intervention to rejuvenate aged HSCs and mitigate hematopoietic decline.

Keywords: aging; drug target; hematopoietic stem cell transplantation; hematopoietic stem cells; stem cells.

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Conflict of interest statement

A.B.D. and S.D.M. and A.A.P. are inventors on patents describing inhibitors of 15-PGDH and their therapeutic uses. These patents have been licensed to Rodeo Therapeutics, which is owned by Amgen.

References

    1. Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: an expanding universe. Cell. 2023;186:243-278. 10.1016/j.cell.2022.11.001 - DOI - PubMed
    1. Campisi J, Kapahi P, Lithgow GJ, Melov S, Newman JC, Verdin E. From discoveries in ageing research to therapeutics for healthy ageing. Nature. 2019;571:183-192. 10.1038/s41586-019-1365-2 - DOI - PMC - PubMed
    1. Kim MJ, Kim MH, Kim SA, Chang JS. Age-related deterioration of hematopoietic stem cells. Int J Stem Cells. 2008;1:55-63. - PMC - PubMed
    1. Geiger H, de Haan G, Florian MC. The ageing haematopoietic stem cell compartment. Nat Rev Immunol. 2013;13:376-389. 10.1038/nri3433 - DOI - PubMed
    1. Schumacher B, Pothof J, Vijg J, Hoeijmakers JHJ. The Central role of DNA damage in the ageing process. Nature. 2021;592:695-703. 10.1038/s41586-021-03307-7 - DOI - PMC - PubMed

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