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Fig. 7 | Biomaterials Research

Fig. 7

From: Fabrication of a three-dimensional bone marrow niche-like acute myeloid Leukemia disease model by an automated and controlled process using a robotic multicellular bioprinting system

Fig. 7

Biocompatibility of 3D BM niche-like AML model for primary AML cells, drug resistance assessment and gene expression profile. (A) Cell viability assessment of primary AML cells after 14 days of 3D culture within IIZK peptide hydrogel. Cells were stained with calcein-AM (green, live cells) and ethidium homodimer-1 (red, dead cells). Left: fluorescent images of cells (scale bar, 200 µM). Right: percentage of cell viability. (B) An analysis of primary AML cell viability under different culture conditions after treatment with AraC. Data represent 5 different AML patients (patients 1–5 from left to right). Primary AML cells in the 3D BM niche-like AML model demonstrated a significant increase in drug resistance compared to other culture conditions (****p < 0.0001,***p < 0.001; **p < 0.01; *p < 0.05). (C & D) RT-qPCR data of AML patient samples. (C) Heatmap illustrating the relative expression in primary AML cells cultured in the 3D BM niche-like AML model and in classical 2D. Red, higher relative expression; green, lower relative expression. (D) Left: commonly upregulated genes in AML cells in the 3D BM niche-like AML model from at least 3 AML paitents compared to the classical 2D culture. Upper right: genes with similar transcription patterns; the average relative quantification (RQ) of genes that had significant alterations in their expression in all patient samples (≥ 2-fold difference). A total of 8 genes were upregulated, and 5 genes were downregulated. Lower right: RQ of NFKB1 and HIF expression in 3D BM niche-like AML model/2D conditions. The average RQ of NFKB1 in the de novo and refractory samples is significantly lower (RQ = 0.8) (p-value < 0.01) compared to relapsed samples (RQ = 2.6). The average RQ of HIF in the de novo and refractory samples is significantly higher (RQ = 2.6) (p-value < 0.05) compared to the relapsed samples (RQ = 1.2).

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