In vivo prostaglandin E2 treatment alters the bone marrow microenvironment and preferentially expands short-term hematopoietic stem cells.

摘要: Microenvironmental signals can determine hematopoietic stem cell (HSC) fate choices both directly and through stimulation of niche cells. In the bone marrow, prostaglandin E(2) (PGE(2)) is known to affect osteoblasts osteoclasts, whereas in vitro it expands HSCs affects differentiation progenitors. We hypothesized that vivo PGE(2) treatment could expand effects on their microenvironment. PGE(2)-treated mice had significantly decreased number trabeculae, suggesting disruption microarchitecture. addition, increased lineage(-) Sca-1(+) c-kit(+) marrow cells without inhibiting differentiation. However, detailed immunophenotyping demonstrated a PGE(2)-dependent increase short-term HSCs/multipotent progenitors (ST-HSCs/MPPs) only. Bone transplanted from versus vehicle-treated donors superior lymphomyeloid reconstitution, which ceased by 16 weeks, also ST-HSCs were preferentially expanded. This was confirmed serial transplantation studies. Thus treatment, probably combination direct microenvironmental actions, absence injury, with no negative impact or long-term HSCs. These novel be exploited clinically donor ST-HSCs, are highly proliferative accelerate recovery after transplantation.