Mesenchymal stem cells from bone marrow attenuated the chronic morphine-induced cAMP accumulation in vitro

Mesenchymal stem cells from bone marrow attenuated the chronic morphine-induced cAMP accumulation in vitro
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骨髓间充质干细胞在体外减弱吗啡诱导的慢性 cAMP 积累

DOI:
10.1016/j.neulet.2018.12.046
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发表时间:
2019-04
影响因子:
2.5
通讯作者:
Qu Tingyu
Qu Tingyu
中科院分区:
医学4区
文献类型:
--
作者:
Yang Hongna;Sun Jinhua;Chen Heng;Wang Feng;Li Yan;Wang Hao;Qu Tingyu

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尽管阿片类药物耐受性是医学中常见的主要挑战,但阿片类药物治疗目前是治疗急性和慢性疼痛的主要方法。慢性吗啡诱导的cAMP蓄积被认为是吗啡耐受和依赖的分子机制之一。在本研究中,我们用视黄酸(RA)将SH-SY 5 Y细胞分化为神经元样细胞,用吗啡预处理这些细胞,并在不同条件下检测其cAMP水平,包括以不同的hMSCs-BM/SH-SY 5 Y比例(1:5,1:25和1:125)与来自骨髓的骨髓间充质干细胞(hMSCs-BM)共培养,通过直接细胞与细胞接触或不与细胞接触,以及通过来自hMSCs-BM的条件培养基(CM)。我们发现,10 μM吗啡慢性处理导致RA分化的SH-SY 5 Y细胞中cAMP上调,而吗啡诱导的cAMP积累通过与hMSCs-BM以较低的细胞比(1:25)和较高的细胞比(1:5)直接细胞与细胞接触而显著减弱。然而,在没有细胞与细胞接触的情况下,在低或高细胞比率下,hMSCs-BM都不能抑制RA分化的SH-SY 5 Y细胞中吗啡诱导的cAMP积累。总之,hMSCs-BM可以通过以较高比率的细胞与细胞接触成功地抑制RA分化的SH-SY 5 Y细胞中吗啡诱导的cAMP上调,这表明hMSCs-BM可以作为有价值的治疗剂,以最大限度地减少吗啡耐受和依赖治疗中药物滥用和成瘾的风险。
Even though opioid tolerance is both a common and a major challenge in medicine, treatment with opioids is currently the primary method used to treat acute and chronic pain. The cAMP accumulation induced by chronic morphine is regarded as one of the molecular mechanisms leading to its tolerance and dependence characteristics. In the present study, we differentiated SH-SY5Y cells into neuron-like cells by retinoic acid (RA), pretreated these cells with morphine, and tested their cAMP levels under different conditions, including co-culture with bone marrow-derived human mesenchymal stem cells from bone marrow (hMSCs-BM) at various hMSCs-BM/SH-SY5Y ratios (1:5, 1:25, and 1:125), by direct cell-to-cell contact or without cell-to-cell contact, and by conditioned medium (CM) from hMSCs-BM. We found that chronic treatment with 10 μM morphine led to cAMP upregulation in those RA-differentiated SH-SY5Y cells while the morphine induced-cAMP accumulation was significantly attenuated by co-culturing with hMSCs-BM by direct cell-to-cell contact at a lower cell ratio (1:25) and a higher cell ratio (1:5). However, at neither the low or higher cell ratios could hMSCs-BM inhibit morphine-induced cAMP accumulation in RA-differentiated SH-SY5Y cells without cell-to-cell contact. In summary, hMSCs-BM can successfully inhibit morphine-induced cAMP up-regulation in RA-differentiated SH-SY5Y cells by cell-to-cell contact at a higher ratio, suggesting that hMSCs-BM may serve as valuable therapeutics to minimize the risk of drug abuse and addiction in the treatment of morphine tolerance and dependence.
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发表时间: 2007-08-01
影响因子: 4.4
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发表时间: 2017-11-29
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