Co-culture with leukemia cells decreases proliferation and increases chemoprotective capacity of normal mesenchymal stromal cells [post]

2020 unpublished
The second hospital of shanxi medical university Wanfang Yang The second hospital of shanxi medical university Yaofang Zhang The second hospital of shanxi medical university Xiuhua Chen The second hospital of Shanxi medical university Fanggang Ren The second hospital of shanxi medical university Jing Xu The second hospital of Shanxi medical university Yanhong Tan The second hospital of shanxi medical university Zhifang Xu The second hospital of shanxi medical university Jianmei Chang The second
more » ... ei Chang The second medical of shanxi medical university Abstract Background Bone marrow mesenchymal stromal cells (BM-MSCs) are essential structural and functional components of the BM microenvironment and play an important role in acute myeloid leukemia (AML) pathogenesis. BM-MSCs isolated from AML patients (AML-MSCs) show distinct signatures from normal BM-MSCs. However, the exact abnormalities of AML-MSCs and the origin of these abnormalities are still unknown. Methods In this study, we evaluated the proliferative activity of AML-MSCs, and the influence of leukemia cells (LCs) on BM-MSCs. These two cell types were co-cultured using an in vitro co-culture system, and the biological functions of AML-MSCs, healthy donor derived MSCs (HD-MSCs), and LC-treated HD-MSCs (LCtrHD-MSCs) were compared by flow cytometry, and CCK-8 and chemotaxis assays. Student t-test (between two groups) and one-way ANOVA (more than 2 groups) were used to compare differences. Pearson correlation coefficients were used to assess correlations between two factors. Results AML-MSCs display a significant proliferative deficiency, which correlates with primary leukemic blast cell counts but not with patients' age. Inhibition of BM-MSC proliferation could be induced by leukemia cells through direct contact. Co-cultured leukemia cells also increase expression of several inflammatory cytokines, and chemokines in BM-MSCs. Furthermore, LCtrHD-MSCs reduced apoptosis, and increased migration and chemoresistance in co-cultured AML cells, comparable with AML-MSCs. Conclusions Our results showed that leukemia cells can induce healthy donor derived BM-MSCs to exhibit AML-MSC-like characteristics and indicated that AML-MSC abnormalities may be partly induced by leukemia cells. Background Acute myeloid leukemia (AML) is a heterogeneous clonal disorder marked by expansion
doi:10.21203/rs.3.rs-16127/v1 fatcat:r7dedd5opbdire5bdma47rbd5y