Nikkhah Hossein, Safarzadeh Elham, Shamsasenjan Karim, Yousefi Mehdi, Lotfinejad Parisa, Talebi Mehdi, Mohammadian Mozhde, Golafshan Farhoud, Movassaghpour Aliakbar
Tabriz University Faculty of Medicine, Hematology and Oncology Research Center, Tabriz, Iran.
Tabriz University Faculty of Medicine, Drug Applied Research Center, Tabriz, Iran.
Turk J Haematol. 2018 Mar 1;35(1):42-48. doi: 10.4274/tjh.2016.0498. Epub 2017 Jun 13.
Mesenchymal stem cells (MSCs) are multipotent stromal cells that can differentiate into a variety of cell types. They control the process of hematopoiesis by secreting regulatory cytokines and growth factors and by the expression of important cell adhesion molecules for cell-to-cell interactions. This investigation was intended to examine the effect of bone marrow (BM)-derived MSCs on the differentiation of HL-60 cells according to morphological evaluation, flow cytometry analysis, and gene expression profile.
The BM-MSCs were cultured in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum (FBS). After the third passage, the BM-MSCs were irradiated at 30 Gy. To compare how the HL-60 cells differentiated in groups treated differently, HL-60 cells were cultured in RPMI-1640 and supplemented with 10% FBS. The HL-60 cells were seeded into six-well culture plates and treated with all-trans-retinoic acid (ATRA), BM-MSCs, or BM-MSCs in combination with ATRA, while one well remained as untreated HL-60 cells. The expression levels of the granulocyte subset-specific genes in the HL-60 cells were assayed by real-time polymerase chain reaction.
Our results revealed that BM-MSCs support the granulocytic differentiation of the human promyelocytic leukemia cell line HL-60.
Based on the results of this study, we concluded that BM-MSCs may be an effective resource in reducing or even preventing ATRA's side effects and may promote differentiation for short medication periods. Though BM-MSCs are effective resources, more complementary studies are necessary to improve this differentiation mechanism in clinical cases.
间充质干细胞(MSCs)是多能基质细胞,可分化为多种细胞类型。它们通过分泌调节性细胞因子和生长因子以及通过表达用于细胞间相互作用的重要细胞粘附分子来控制造血过程。本研究旨在根据形态学评估、流式细胞术分析和基因表达谱来检测骨髓(BM)来源的MSCs对HL-60细胞分化的影响。
将BM-MSCs培养于补充有10%胎牛血清(FBS)的杜氏改良 Eagle 培养基中。传代三次后,将BM-MSCs以30 Gy进行辐照。为比较HL-60细胞在不同处理组中的分化情况,将HL-60细胞培养于补充有10% FBS的RPMI-1640培养基中。将HL-60细胞接种到六孔培养板中,并用全反式维甲酸(ATRA)、BM-MSCs或BM-MSCs与ATRA联合处理,同时有一孔作为未处理的HL-60细胞。通过实时聚合酶链反应检测HL-60细胞中粒细胞亚群特异性基因的表达水平。
我们的结果显示,BM-MSCs支持人早幼粒细胞白血病细胞系HL-60的粒细胞分化。
基于本研究结果,我们得出结论,BM-MSCs可能是减少甚至预防ATRA副作用的有效资源,并且可能在短疗程用药时促进分化。尽管BM-MSCs是有效的资源,但仍需要更多的补充研究来改善临床病例中的这种分化机制。