Experimental Hematology | VOL. 88
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3079 – MURINE WHOLE BONE MARROW MAY CONTAIN A NONCONVENTIONAL POPULATION OF LONG-TERM MULTI-LINEAGE REPOPULATING CELLS WITH ALTERED SUSCEPTIBILITY TO AGING

Publication Date Aug 1, 2020

Abstract

Studies in hematopoietic aging have shown that classically defined, highly purified hematopoietic stem cells (HSCs) increase in number but have impaired function and exhibit myeloid skewing. However, we identified a cycling population of HSCs in young mice that appear to be preferentially lost during standard HSC isolations and therefore poorly represented within the purified HSC population. Here, we sought to determine how aging may alter this total HSC population in unseparated murine whole bone marrow (WBM). In limit dilution competitive bone marrow transplantation, we found that, at 6 months post-transplant, old (24-26-mo-old) WBM had a 4-fold increase in functional HSCs compared to young (6-8-wk-old) WBM. Unlike purified old HSCs, old WBM showed only minimal myeloid skewing (myeloid: 26%±11% of old donor peripheral blood vs.19%±16% of young donor peripheral blood; average percent donor peripheral blood ± SD; n=26 mice). Interestingly, in two experiments, old WBM retained full engraftment capacity in secondary transplant with no myeloid skewing, while in a third experiment, old WBM engraftment was significantly decreased when compared to young WBM (15%±9% vs. 57%±3%, respectively; average% donor chimerism ± SD), and exhibited clear myeloid skewing (myeloid: 65%±7% of old donor peripheral blood vs. 20%±10% of young donor peripheral blood; 4-5mice/grp/exp). These data suggest that only those old HSCs in unseparated WBM with high engraftment capacity may retain youthful myeloid/lymphoid ratio patterns. Preliminary data in f...

Concepts
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Whole Bone Marrow
Myeloid Skewing
Hematopoietic Stem Cells
Donor Peripheral Blood
Hematopoietic Stem Cells Population
Secondary Transplant
Lineage Fate Decisions
Functional Hematopoietic Stem Cells
Engraftment Capacity
Hematopoietic Aging

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