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PGE2, EGF, FLT3L and TPO in human hematopoiesis
Sublethal irradiation cleared most of human hematopoi- etic cells and daily dmPGE2 administration did not result in their protection (Figure 4A and B). In contrast, etopo- side treatment appeared more toxic for murine hematopoietic cells (Online Supplementary Figure S4A). When etoposide was combined with dmPGE2 treatment, we observed enrichment of human CD45+ cells indicating
some survival advantages over murine cells (Figure 4C and E). However, this was not reflected by increased absolute numbers of human cells (Figure 4D and F). Interestingly, dmPGE2 administration together with total body irradiation or etoposide treatment provoked pro- fuse and nearly fatal diarrhea making such an approach unusable.
AB
CD
EF
GH means±Standard Error of Mean (SEM) of n=4-7 animals from 3 inde- pendent experiments. Mann-Whitney test, *P≤0.05; **P≤0.01; ***P≤0.001. (E-H) Treatment with human TPO and FLT3L was given for 14 days and % human CD45+ cells was determined in BM (E) and spleen (G). Cell counts of human CD45+ cells were determined (F and H). Bars rep- resent means±SEM of 5-11 animals from 3 independent experiments.
Figure 5. Mild beneficial effects of FLT3L and thrombopoietin (TPO) in vivo. (A-D) Human CD34+ cells were transplanted into sublethally irradiat- ed Rag2−/−γc−/− mice. Four weeks later, mice were irradiated with 3 Gy or left untreated. Mice that were irra- diated received daily injections of human TPO and/or FLT3L. Eight days after irradiation, mice were sacrificed and % human CD45+ cells were deter- mined in bone marrow (BM) (A) and spleen (C). Human CD45+ cell num- bers were determined in BM (B) and spleen (D). Bars represent
Mann-Whitney test, **P≤0.01; ***P≤0.001.
*P≤0.05;
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