An actively regenerating hematopoietic environment enhances the function of transplanted stem cells

Hematopoietic cell transplantation is a curative treatment for many hematologic malignancies and selected non-malignant hematologic, immunologic, and genetic disorders. Hematopoietic reconstitution is initially driven mainly by progenitor cells with limited long-term repopulating capacity, whereas reconstitution of the hematopoietic stem cell (HSC) compartment occurs more slowly. We hypothesized that this period of active hematopoietic regeneration may provide a favorable environment for the engraftment of subsequently transplanted HSCs. Mice underwent sequential transplantation with bone marrow cells carrying different CD45 allotypes. Long-term donor contribution was assessed in immature bone marrow cell populations and peripheral blood. HSCs engrafted during active hematopoietic regeneration showed superior long-term reconstitution, contributing a greater proportion of hematopoietic and immune cells than HSCs engrafted after myeloablative conditioning. An actively regenerating hematopoietic environment engrafts transplanted HSCs and enhances their long-term function in the production of blood and immune cells. These findings demonstrate that the timing and environmental context of engraftment are strongly associated with long-term stem cell performance. The mechanisms responsible for this effect remain to be determined. These findings have direct clinical potential.