MON-740 Abaloparatide Increases Bone Marrow Stromal Cells And Decreases Features Of Hematopoietic Aging In Old Male Mice

Abstract Disclosure: R. Lakony: None. N. Vdovichenko: None. Y. Esaki: None. A. Tyrlik: None. Z. Jin: None. J. Zhang: None. C. Caballero: None. S. Patel: None. E.R. Quarato: None. N.A. Salama: None. Y. Kawano: None. L. LaMere: None. J.L. Liesveld: None. L.M. Calvi: None. Maintenance and differentiation of hematopoietic stem cells (HSCs) are regulated by multiple cells in the bone marrow microenvironment (BMME), including osteolineage cells, bone marrow stromal cells (BMSCs), and endothelial cells. For instance, Calvi et al. has demonstrated that osteolineage cells participate in the expansion of HSCs through activation of parathyroid hormone (PTH) receptors in their experiment in which constitutive activation of the PTH1 receptors in osteoblasts as well as intermittent administration of PTH (1-34) increased the number of HSCs in 6 to 8-week-old mice male (1). In addition to supporting HSCs, BMSCs also have immunosuppressive and anti-inflammatory effects via cytokine modulation and exome signaling. Aging is known to promote myeloid lineage expansion (myeloid skewing), increase megakaryocyte-biased HSCs that express CD41, and decrease in lymphoid lineage. In our experiment, abaloparatide increased the number of BMSCs and decreased the phenotype of hematopoietic aging. Eighteen-month-old male mice were treated with either abaloparatide 80 ug/kg or saline vehicle daily intraperitoneally for 28 days. DXA scan performed at baseline, 2 weeks (mid treatment) and at 4 weeks (end of treatment) showed expected anabolic effects in the abaloparatide treated mice, particularly in the total bone mineral density. Bone marrow specimens were obtained from 2 pelvises, 2 femurs, and 2 tibiae and analyzed with Flow cytometry. Abaloparatide increased the live percentage and absolute number of osteoblasts, bone marrow stromal cells as well as immature stromal cells such as PaS and Paav, known to be critical niche populations that support and regulate HSCs. The live percentage of short-term HSCs was increased in the abaloparatide-treated mice compared with vehicle-treated mice as shown before. In addition, several age-associated hematopoietic changes were reversed by abaloparatide treatment, including decreased neutrophils and CD41-positive multipotent progenitors, suggesting that abaloparatide diminished the myeloid skewing of hematopoiesis that is characteristic of inflammaging. These results indicate that the abaloparatide may provide beneficial effects not only to reverse skeletal bone loss in aging, but also improving hematopoiesis and mitigating inflammaging. References: 1. Calvi LM, et al. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 2003 Oct 23;425(6960):841-6. Presentation: Monday, July 14, 2025