Systemic delivery of mesenchymal stem cells condition media in repeated doses acts as magic bullets in restoring IFN-γ/IL-4 balance in asthmatic rats
Systemic delivery of mesenchymal stem cells condition media in repeated doses acts as magic bullets in restoring IFN-γ/IL-4 balance in asthmatic rats
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DOI：
10.1016/j.lfs.2018.09.049
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发表时间：
2018-11-01
期刊：
影响因子：
6.1
通讯作者：
Ahmadi, Mahdi
中科院分区：
文献类型：
--
作者：
Keyhanmanesh, Rana;Rahbarghazi, Reza;Ahmadi, Mahdi
关于干细胞应用的最新优势，考虑到之前报道的干细胞移植后的担忧，间充质干细胞衍生的条件培养基（MSC-CM）可能是一种比目前基于干细胞的再生疗法更安全、更有效的潜在方法。主要方法：雄性大鼠分为4个实验组（n=6）；健康大鼠（C组）、OVA致敏大鼠（S组）、OVA致敏大鼠单次静脉注射50 μ l CM (S组+ SD-CM)， OVA致敏大鼠多次静脉注射50 μ l CM （S组+ RD-CM）。在过敏原攻击2周后，通过监测T-bet、GATA-3、IL-4和ifn - γ基因的转录以及哮喘肺组织的病理变化，研究单次和多次全身给药CM的治疗效果。进一步检测血清中IL-4、ifn - γ水平及ifn - γ /IL-4比值。主要发现：我们的数据显示，全身重复剂量引入CM可以通过调节肺组织中T-bet和GATA-3的表达和白细胞介素水平，显著减轻ova致敏大鼠的病理损伤（p < 0.001 ~ p < 0.05）。相反，单剂量CM不产生任何有益效果。意义：总的来说，我们表明，在ova致敏的雄性大鼠中，反复给药而不是单次给药CM可能是改善哮喘变化的策略方法，可能是通过调节T-bet和GATA-3的表达来调节初始CD4 T细胞向Th1/Th2效应细胞的分化。
Aims: With respect to recent advantage in stem cell application, given the concern reported previously after stem cell transplantation, mesenchymal stem cell-derived conditioned media (MSC-CM) could be a potential approach to guarantee more safety and efficient outcomes than the current stem cell-based regenerative therapies.Main methods: Male rats were assigned into four experimental groups (n=6); healthy rats (C group), OVA sensitized rats (S group), OVA sensitized rats received a single dose of 50 mu l CM intravenously (S group + SD-CM) and OVA sensitized rats received repeated doses of 50 mu l CM intravenously (S group + RD-CM). Two weeks post-allergen challenge, the therapeutic effects of systemic administrated CM in single and repeated dosages were investigated by monitoring the transcription of T-bet, GATA-3, IL-4 and IFN-gamma genes along with pathological changes in asthmatic lung tissue. IL-4 and IFN-gamma levels and IFN-gamma/IL-4 ratio were further evaluated in sera.Key findings: Our data revealed that the systemic introduction of CM in repeated dosages could significantly reduce pathological injures in OVA-sensitized rats by the modulation of expression of T-bet and GATA-3 in lung tissues and interleukins levels (p < 0.001 to p < 0.05). In contrary, CM in single dosage did not yield any beneficial effect.Significance: Overall, we indicated that systemic administration of CM in repeated dosages, but not in single dose, could be strategic approach in amelioration of asthmatic changes, presumably by the regulating the differentiation of naive CD4 T cells into Th1/Th2 effector cells via modulation of T-bet and GATA-3 expression in OVA-sensitized male rats.