Understanding Bone Marrow Interactions w\hich Drive Aging of Hematopoietic Stem Cells

Bone marrow(BM) niche aging contributes to hematopoietic stem cell(HSC) dysfunction and consequent impaired tissue homeostasis in the elderly, but the cellular interactions remain unclear. I hypothesize that aging of BM niche cells drive HSC aging by altering their differentiation capacity. To evaluate old microenvironmental influence on HSCs, young Sca-1+ BM stem cells were transplanted into old(Y-O) compared to young(Y-Y) irradiated mice and showed increased BM cellularity(p=0.01) and % of Lin-/Sca-1+/cKit+HSCs(LSKs)(p=0.003), similar to old BM. To mimic cell interactions in the BM, F4/80+/CD11b+/CD45+ immune, Sca-1+/PDGRFα+/CD90⁻ stromal, and CD90+/CD29+/Sca-1+ bone-forming niche cells were isolated from young and old BM. Co-culture with young LSKs showed LSK expansion(p=0.04) by old niche cells, reduction in stemenss by old stromal cells, and enhanced myeloid differentiation and Lin- colony production in Methocult medium by old immune cells. BM niche cells are key players in HSC differentiation, which are potential targets for BM rejuvenation therapy in the elderly.