Figure 4.
Figure 4. Assessment of the self-renewal potential of engrafting AML cells in scaffolds coated with human versus musine MSCs by serial transplantation of 3 AML samples. (A) Schematic representation of the generation of mouse models with scaffolds coated with huBM-sc vs muBM-sc. (B) Plots showing percentage of engraftment of donor human CD45+ cells in the scaffolds in huBM-sc vs muBM-sc models, using patient samples with adverse, intermediate, and favorable risk. Engraftment values from 8 scaffolds in 2 mice (mouse 1 indicated with red symbols and mouse 2 indicated with black symbols) for each AML sample are expressed as mean ± SEM. (C) For secondary transplantations, leukemic cells harvested from the scaffold of a primary huBM-sc or muBM-sc mouse were injected into the scaffolds of secondary recipient huBM-sc or muBM-sc mice. Kaplan-Meier plots are shown. Significantly better secondary engraftment for the intermediate-risk sample #18 was shown in the huBM-sc model, whereas significantly better engraftment for the favorable-risk sample (#33) was already observed in the primary transplantations. (D) Ceramic scaffold implants coated with murine MSCs generate an ectopic hematopoietic niche. H&E stains of different murine implants before inoculation with AML cells. As shown the scaffolds are covered by murine bone (b) with vascularization (v), resulting in the support of the murine hematopoiesis in Rag2−/−γc−/− mice. *P < .05. n.s., not significant.

Assessment of the self-renewal potential of engrafting AML cells in scaffolds coated with human versus musine MSCs by serial transplantation of 3 AML samples. (A) Schematic representation of the generation of mouse models with scaffolds coated with huBM-sc vs muBM-sc. (B) Plots showing percentage of engraftment of donor human CD45+ cells in the scaffolds in huBM-sc vs muBM-sc models, using patient samples with adverse, intermediate, and favorable risk. Engraftment values from 8 scaffolds in 2 mice (mouse 1 indicated with red symbols and mouse 2 indicated with black symbols) for each AML sample are expressed as mean ± SEM. (C) For secondary transplantations, leukemic cells harvested from the scaffold of a primary huBM-sc or muBM-sc mouse were injected into the scaffolds of secondary recipient huBM-sc or muBM-sc mice. Kaplan-Meier plots are shown. Significantly better secondary engraftment for the intermediate-risk sample #18 was shown in the huBM-sc model, whereas significantly better engraftment for the favorable-risk sample (#33) was already observed in the primary transplantations. (D) Ceramic scaffold implants coated with murine MSCs generate an ectopic hematopoietic niche. H&E stains of different murine implants before inoculation with AML cells. As shown the scaffolds are covered by murine bone (b) with vascularization (v), resulting in the support of the murine hematopoiesis in Rag2−/−γc−/− mice. *P < .05. n.s., not significant.

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