Mesenchymal Stem Cells as a Cell-Based Therapeutic Strategy Targeting the Telomerase Activity of KG1 Acute Myeloid Leukemia Cells

  • Ezzatollah Fathi Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran
  • Raheleh Farahzadi Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Keywords: Mesenchymal stem cells; Acute myeloid leukemia; Telomerase activity; Telomere length; Extracellular signal regulated kinase (ERK) signaling pathway

Abstract

A predominant challenge in the discovery approach to curative leukemia is investigating the effect of mesenchymal stem cells (MSCs) on leukemic cells. We aimed to investigate the role of MSCs in targeting telomerase enzyme and consequently telomere length of leukemic cells. For this purpose, the KG1 cell as leukemia cell line was co-cultured with MSCs in the trans-well system. After seven days of co-culture, KG1 cells were collected, and telomerase activity, telomere length, and hTERT gene expression were analyzed by PCR-ELISA TRAP assay and real-time PCR, respectively. Also, the potentially involved ERK pathway was analyzed at gene and protein levels by real time PCR and flow cytometry, respectively. It was found that MSCs caused a significant decrease in telomerase activity, telomere length, and hTERT gene expression. The following results showed that MSCs resulted in a significant decrease in the ERK expression levels. It can be concluded that the co-culture of MSCs with KG1 cells be involved in the telomerase targeting via ERK signaling pathways. This study concluded that the co-culture of MSCs with AML leukemic cells could secrete a significant amount of cytokines that cause to inhibit the proliferation of AML cell lines via ERK signaling pathway. The recognition of cytokines as well as growth factors involved in the anti-proliferative effect of MSCs requires further investigation. This effect as a therapeutic strategy could be considered in the basic experimental studies.

Published
2022-02-23
Section
Articles