ABSTRACT
Background: One of the most significant problems in the treatment of leukemia is the expansion of resistance to chemotherapeutic agents. Therefore, assessing the drug resistance and especially the drug resistance genes of leukemic cells is important in any treatment. The impact of Mesenchymal Stem Cells [MSCs] and hypoxic condition have been observed in the biological performance of majority of leukemic cells
Methods: MOLT-4 cells were co-cultured with MSCs in the hypoxic condition induced by Cobalt Chloride [CoCl2] for 6 and 24 hr. Then, apoptosis of cells was analyzed using annexin-V/PI staining and expression of the drug resistance genes including MDR1, MRP, and BCRP along with apoptotic and anti-apoptotic genes, including BAX and BCL2, was evaluated by real-time PCR
Results: The hypoxic condition for MOLT-4 cells co-cultured with MSCs could significantly increase the expression of MDR1 and BCRP genes [p<0.05] which are involved in drug resistance. Also, the results indicated that this condition significantly increases the expression of BCL2 [p<0.05] and reduces the apoptosis in MOLT- 4 cells co-cultured with MSCs in the hypoxic condition
Conclusions: These effects can demonstrate the important role of hypoxia and MSCs on the biological behavior of Acute Lymphoblastic Leukemia [ALL] cells that may lead to particular treatment outcomes
ABSTRACT
Objective: Bone marrow mesenchymal stem cells [BMMSCs] reside in the bone marrow and control the process of hematopoiesis. They are an excellent instrument for regenerative treatment and co-culture with hematopoietic stem cells [HSCs]
Materials and Methods: In this experimental study, K562 cell lines were either treated with butyric acid and co-cultured with MSCs, or cultivated in a conditioned medium from MSCs plus butyric acid for erythroid differentiation. We used the trypan blue dye exclusion assay to determine cell counts and viability in each group. For each group, we separately assessed erythroid differentiation of the K562 cell line with Giemsa stain under light microscopy, expression of specific markers of erythroid cells by flowcytometry, and erythroidspecific gene expressions by real-time polymerase chain reaction [RT-PCR]
Results: There was enhandced erythroid differentiation of K562 cells with butyric acid compared to the K562 cell line co-cultured with MSCs and butyric acid. Erythroid differentiation of the K562 cell line cultivated in conditioned medium with butyric acid was higher than the K562 cell line co-cultured with MSCs and butyric acid, but less than K562 cell line treated with butyric acid only
Conclusion: Our results showed that MSCs significantly suppressed erythropoiesis. Therefore, MSCs would not be a suitable optimal treatment strategy for patients with erythroid leukemia