Valizadeh Armita, Ahmadzadeh Ahmad, Saki Ghasem, Khodadadi Ali, Teimoori Ali
Physiology Research Center, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran E-mail :
Asian Pac J Cancer Prev. 2015;16(18):8533-9. doi: 10.7314/apjcp.2015.16.18.8533.
B-cell chronic lymphocytic leukemia B (B-CLL), the most common type of leukemia, may be caused by apoptosis deficiency in the body. Adipose tissue-derived mesenchymal stem cells (AD-MSCs) as providers of pro-apoptotic molecules such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), can be considered as an effective anti-cancer therapy candidate. Therefore, in this study we assessed the role of tumor necrosis factor-producing mesenchymal stem cells oin apoptosis of B-CLL cells resistant to fludarabine- based chemotherapy.
In this study, after isolation and culture of AD-MSCs, a lentiviral LeGO-iG2-TRAIL-GFP vector containing a gene producing the ligand pro-apoptotic with plasmid PsPAX2 and PMDG2 virus were transfected into cell-lines to generate T293HEK. Then, T293HEK cell supernatant containing the virus produced after 48 and 72 hours was collected, and these viruses were transduced to reprogram AD-MSCs. Apoptosis rates were separately studied in four groups: group 1, AD-MSCs-TRAIL; group 2, AD-MSCs-GFP; group 3, AD-MSCs; and group 4, CLL.
Observed apoptosis rates were: group 1, 42 ± 1.04%; group 2, 21 ± 0.57%; group 3, 19± 2.6%; and group 4, % 0.01 ± 0.01. The highest rate of apoptosis thus occurred ingroup 1 (transduced TRAIL encoding vector). In this group, the average medium-soluble TRAIL was 72.7pg/m and flow cytometry analysis showed a pro-apoptosis rate of 63 ± 1.6%, which was again higher than in other groups.
In this study we have shown that tumor necrosis factor (TNF) secreted by AD-MSCs may play an effective role in inducing B-CLL cell apoptosis.
B 细胞慢性淋巴细胞白血病 B（B-CLL）是最常见的白血病类型，可能由机体凋亡缺陷引起。脂肪组织来源的间充质干细胞（AD-MSCs）作为促凋亡分子如肿瘤坏死因子相关凋亡诱导配体（TRAIL）的提供者，可被视为一种有效的抗癌治疗候选者。因此，在本研究中，我们评估了产生肿瘤坏死因子的间充质干细胞在对基于氟达拉滨的化疗耐药的 B-CLL 细胞凋亡中的作用。
在本研究中，分离培养 AD-MSCs 后，将含有产生促凋亡配体基因的慢病毒 LeGO-iG2-TRAIL-GFP 载体与质粒 PsPAX2 和 PMDG2 病毒转染到细胞系中以生成 T293HEK。然后，收集 48 小时和 72 小时后产生的含病毒的 T293HEK 细胞上清液，并将这些病毒转导以重编程 AD-MSCs。在四组中分别研究凋亡率：第 1 组，AD-MSCs-TRAIL；第 2 组，AD-MSCs-GFP；第 3 组，AD-MSCs；第 4 组，CLL。
观察到的凋亡率为：第 1 组，42±1.04%；第 2 组，21±0.57%；第 3 组，19±2.6%；第 4 组，0.01±0.01%。因此，凋亡率最高的是第 1 组（转导编码 TRAIL 的载体）。在该组中，平均培养基可溶性 TRAIL 为 72.7pg/ml，流式细胞术分析显示促凋亡率为 63±1.6%，再次高于其他组。
在本研究中我们表明，AD-MSCs 分泌的肿瘤坏死因子（TNF）可能在诱导 B-CLL 细胞凋亡中发挥有效作用。
