Targeting the Proliferation Inhibition of Chronic Myeloid Leukemia Cells by Bone Marrow Derived-Mesenchymal Stem Cells via ERK Pathway as a Therapeutic Strategy

Abstract

Bone marrow-derived mesenchymal stem cells (BMSCs) are of specific attention due to their potential clinical use in cell transplantation. These cells could secrete cytokines and growth factors upon stimulation or suppression in regenerative medicine. This study was to evaluate the influence of BMSCs on the proliferation of K562 cells as chronic myeloid leukemia (CML) cell lines through the ERK pathway. For this purpose, BMSCs were extracted from Rattus Norvegicus and were co-cultured with K562 cells. In the following, at the end of the 7th day, the K562 cell was collected and subjected to ERK protein expression measurement as well as ERK gene expression by flow-cytometry and real time-PCR, respectively. Also, the cell proliferation and PDT of K562 cells were measured in the control and experimental groups. The results were shown that BMSCs were positive for mesenchymal (CD44 and CD90) and negative for hematopoietic (CD34 and CD56) markers. In addition, it was shown that BMSCs mediated CML cell line proliferation arrest via a significant reduction of the ERK protein expression in the co-culture groups versus in the K562 cell line control group. Taken together, the data concluded that the co-culture of BMSCs with CML cell lines could secrete a substantial amount of cytokines and growth factors, thus inhibiting the proliferation of CML cell lines via the ERK signaling pathway. The identity of molecules, cytokines, and growth factors involved in the anti-proliferative effect of bone marrow-derived MSCs require further investigation, and this effect could important in the basic experimental study as a therapeutic strategy.