Fig. 4: Effects of a treatment with IFN-γ, IL-1β or LPS from day 7 to day 17 on lineage differentiation.

Sampled cell counts are plotted relative to the untreated control condition of the same donor and day. Mean relative cell count values +/− s.e.m of three CD34+ cell donors (large symbols) and two to three chips (small symbols) each are shown. Statistical comparison of means was performed on log-transformed count data of the treatment phase (day 10 + day 17), the recovery phase (day 24 + day 31) and the ceramic scaffold by a repeated measures two-way ANOVA plus Dunnett’s post hoc test with the untreated condition of each day as control condition (N = 3 donors, DFn = 6, DFd = 12, F(ery) = 16.79, F(NC Mono) = 4.867, F(Granu) = 11.89). Statistical significance was defined as ****p < 0.0001, ***p < 0.001, **p  <  0.01, *p  <  0.05 and ns (p  >  0.05). A Sampled relative cell counts of erythroid cell in circulation (left plot) and in the ceramic scaffold at the end of cultivation (right plot). B Exemplary flow cytometry dot plot (CD71 vs CD235) of one circuit treated with IL-1β in comparison to one untreated circuit at day 17. C Sampled relative cell counts of NK cells in circulation (left plot) and in the ceramic scaffold at the end of cultivation (right plot). One donor did not produce NK-cells so only values from two CD34+ cell donors are shown. D Exemplary flow cytometry dot plot of lymphoid cell populations (CD56 vs CD10) of one circuit treated with IFN-γ in comparison to one untreated circuit at day 31. E Sampled cell counts of non-classical monocytes in circulation (left plot) and in the ceramic scaffold at the end of cultivation (right plot). F Exemplary flow cytometry dot plot of granulocytes (CD16 vs CD13) of one circuit treated with LPS in comparison to one untreated circuit at day 24. G Sampled cell counts of granulocytes in circulation (left plot) and in the ceramic scaffold at the end of cultivation (right plot). H Exemplary flow cytometry dot plot of monocytes (CD13 vs CD16) of one circuit treated with IL-1β in comparison to one circuit from the same donor without treatment at day 17 of the assay. I Concentrations of the inflammatory factors IL-23, G-CSF, TNFa, MCP-1, IL-6, and IL-1β in the cell culture medium over time. For comparison of cytokine concentration between groups, area under curve values were analyzed and compared with a repeated measures one-way ANOVA and Dunnett’s multiple comparisons test (N = 3 donors, DFn = 3, DFd = 6, F(IL-23) = 303.7, F(G-CSF) = 593.5, F(TNFa) = 42.65, F(MCP1) = 160.3, F(IL-6) = 114.8. F(IL-1β) = 1876).