Table 1.
Clinical outcome of therapeutic HSCT in NHD13 mice with MDS.
Table 2.
Clinical outcome of A-HSCT with induced GVHD/GVL.
Fig 1.
Syngeneic hematopoietic stem cell transplant (S-HSCT) as therapy for MDS.
(A) Schematic illustration of S-HSCT experiment, using myeloablative (10 Gy) or non-myeloablative (6.5 Gy) total body irradiation as a conditioning regimen (B) Representative FACS profiles of individual recipients at 16 and 26 weeks post-transplant. CD45.2+ indicates cells derived from the host. (C) CD45.2+ cells from individual recipients; increasing CD45.2+ cells indicate relapse of host (MDS-derived) hematopoiesis. (D) Hemoglobin changes following S-HSCT. (E) MCV, Mean corpuscular volume. (F) PLT, platelet count. (G) ANC, absolute neutrophil count. (H) Survival curve after HSCT. The sword symbol indicates death of the recipient.
Fig 2.
Evaluation of allogeneic HSCT (A-HSCT) using the NHD13 model of MDS.
(A) Schematic illustration of AHSCT experiment. (B) Engraftment of donor cells was evaluated using an anti-Ly9.1 antibody. The dotted line indicates Ly9.1 positivity (79.9 ± 2.5%) in the peripheral blood of 5 healthy C3H.sw donor mice, as a reference for full donor chimerism. (C) HGB, hemoglobin. (D) MCV, Mean corpuscular volume. (E) PLT, platelet count. (F) ANC, absolute neutrophil count. (G) WBC, white blood cell count. (H) Survival curve for this cohort only (n = 4). Data presented here is representative of three independent experiments; complete data for all experiments is presented in S3 Fig.
Fig 3.
Overall survival and cumulative incidence of relapse.
(A) Log RANK test for Non-HSCT vs S-HSCT, p = 0.0013; Non-HSCT vs A- HSCT, p = 0.0054; Allo HSCT vs Syn HSCT, p = 0.7373. Non-HSCT NHD13 refers to NHD13 transgenic mice not subjected to myeloablative irradiation and HSCT. WT-HSCT refers to WT recipient mice transplanted with WT syngeneic BMNC following myeloablative irradiation. (B) Cumulative incidence of relapse for S-HSCT and A-HSCT.
Fig 4.
Effect of GVHD using the NHD13 A-HSCT model.
(A) GVHD was induced by transplantation of splenocytes with BMNC. GVHD score vs time for individual recipients; the values for #227 and #235 are identical and thus the curves are superimposed on one another(B) Cumulative incidence of severe GVHD or relapse. Mice were euthanized when they displayed clinical signs of disease such as lethargy, tachypnea, or hunched posture. (C) Survival curve comparison of Non-HSCT NHD13, A-HSCT and A-HSCT + Splenocytes. Non-HSCT NHD13 refers to NHD13 transgenic mice not subjected to irradiation and HSCT.