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在不同培养条件下维持的神经干/祖细胞会改变单核细胞分化为树突状细胞的能力。

Neural stem/progenitor cells maintained under different culture conditions alter differentiation capacity of monocytes to generate dendritic cells.

作者信息

Lupatov Alexey Yu, Poltavtseva Rimma A, Bystrykh Oxana A, Yarygin Konstantin N, Sukhikh Gennady T

机构信息

Institute of Biomedical Chemistry, Moscow, Russia.

Research Center of Obstetrics, Gynecology and Perinatology, Moscow, Russia.

出版信息

J Stem Cells Regen Med. 2017 Dec 18;13(2):54-61. doi: 10.46582/jsrm.1302009. eCollection 2017.

Abstract

Cell therapy of the nervous system disorders using neural stem/progenitor cells (NSPCs) proved its efficacy in preclinical and pilot clinical studies. The mechanisms of the beneficial effects of NSPCs transplantation include replacement of damaged cells, paracrine activation of the regeneration, and immunomodulation. Detailed assessment of NSPCs-induced immunomodulation can contribute to better control of autoimmune reactions and inflammation in patients with neurodegenerative diseases. Interactions of NSPCs with dendritic cells (DCs), the key players in the induction of the immune system response to antigens are of particular interest. Here, we demonstrate that co-culturing of monocytes with NSPCs obtained and grown utilizing serum-containing medium instead of growth factor-containing serum-free medium, results in total suppression of monocyte differentiation into DCs. The effect is similar to the action of mesenchymal stem cells (MSCs). No significant effect on DCs maturation was observed. Cultures of NSPCs set up and maintained in serum-free medium have no influence on monocyte differentiation and DCs maturation. Therefore, the effects of NSPCs upon DC differentiation from monocytes strongly depend on culture conditions, whereas the molecular marker expression patterns are similar in both types of NSPCs cultures. In broader prospective, it means that cells with almost identical phenotypes can display opposite immunological properties depending upon culture conditions. It should be taken into account when developing NSPCs-based cell products for regenerative medicine.

摘要

使用神经干/祖细胞(NSPCs)对神经系统疾病进行细胞治疗已在临床前和临床试验研究中证明了其有效性。NSPCs移植产生有益效果的机制包括受损细胞的替代、再生的旁分泌激活以及免疫调节。对NSPCs诱导的免疫调节进行详细评估有助于更好地控制神经退行性疾病患者的自身免疫反应和炎症。NSPCs与树突状细胞(DCs)的相互作用尤其令人感兴趣,树突状细胞是免疫系统对抗抗原反应诱导中的关键参与者。在此,我们证明,将单核细胞与使用含血清培养基而非含生长因子的无血清培养基获取并培养的NSPCs共培养,会导致单核细胞向DCs的分化完全受到抑制。该效应与间充质干细胞(MSCs)的作用相似。未观察到对DCs成熟有显著影响。在无血清培养基中建立并维持的NSPCs培养物对单核细胞分化和DCs成熟没有影响。因此,NSPCs对单核细胞向DCs分化的影响强烈依赖于培养条件,而两种类型的NSPCs培养物中分子标志物的表达模式相似。从更广泛的前景来看,这意味着具有几乎相同表型的细胞根据培养条件可表现出相反的免疫特性。在开发基于NSPCs的再生医学细胞产品时应考虑到这一点。

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