Myelosuppressive conditioning is required to achieve engraftment of pluripotent stem cells contained in moderate doses of syngeneic bone marrow.

摘要: We have investigated the requirement for whole body irradiation (WBI) to achieve engraftment of syngeneic pluripotent hematopoietic stem cells (HSCs). Recipient B6 (H-2b; Ly-5.2) mice received various doses WBI (0 3.0 Gy) and were reconstituted with 1.5 x 10(7) T-cell-depleted (TCD) bone marrow (BMCs) from congenic Ly-5.1 donors. Using anti-Ly-5.1 anti-Ly-5.2 monoclonal antibodies flow cytometry, origins lymphoid myeloid reconstituting animals observed over time. Chimerism was at least initially detectable in all groups. However, between 3 Gy minimum dose required permit induction long-term (at 30 weeks), multilineage mixed chimerism 100% recipient mice. In these mice, stable reconstitution approximately 70% 90% donor-type lymphocytes, granulocytes, monocytes observed, suggesting that HSC achieved. About 50% conditioned showed evidence donor engraftment. Although low levels detected untreated 0.5-Gy-irradiated recipients early post-BM transplantation (BMT) period, disappeared completely by 12 20 weeks post-BMT. BM colony assays adoptive transfers into secondary lethally irradiated confirmed absence progenitors HSCs, respectively, originally only 0.5 WBI. These results suggest HSCs cannot readily engraft unless host sustain a significant level injury, as is induced also attempted determine duration permissive period Stable uniformly established 3-Gy-irradiated Ly-5.2 when BMC injected within 7 days irradiation, repair damaged or loss factors stimulating may prevent after day 7.