Human bone marrow-derived mesenchymal stromal cells cultured in serum-free media demonstrate enhanced antifibrotic abilities via prolonged survival and robust regulatory T cell induction in murine bleomycin-induced pulmonary fibrosis.
Human bone marrow-derived mesenchymal stromal cells cultured in serum-free media demonstrate enhanced antifibrotic abilities via prolonged survival and robust regulatory T cell induction in murine bleomycin-induced pulmonary fibrosis.
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在无血清培养基中培养的人骨髓源间充质间质细胞通过延长存活时间和强大的调节性T细胞诱导，在博莱霉素诱导的小鼠肺纤维化中表现出增强的抗纤维化能力。
DOI：
10.1186/s13287-021-02574-5
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发表时间：
2021-09-16
影响因子：
7.5
通讯作者：
Hattori N
中科院分区：
文献类型：
--
作者：
Takao S;Nakashima T;Masuda T;Namba M;Sakamoto S;Yamaguchi K;Horimasu Y;Miyamoto S;Iwamoto H;Fujitaka K;Hamada H;Takahashi S;Nakashima A;Hattori N
骨髓间充质干细胞（MSCs）是一种潜在的治疗肺纤维化的工具。然而，使用血清的离体MSC扩增在接受者中造成有害免疫应答或未知病原体感染的风险。因此，在无血清培养基中培养的MSC（SF-MSC）对于临床环境是理想的;然而，它们在肺纤维化中的功效是未知的。在这里，我们研究了SF-MSCs对博来霉素诱导的肺部炎症和纤维化的影响，与含血清培养基中培养的MSCs（S-MSCs）相比。使用RNA序列分析在体外表征SF-MSC和S-MSC。使用博来霉素诱导的肺纤维化的鼠模型研究SF-MSC疗法的体内动力学和功效。对于正态分布的数据，分别使用Student t检验和单向重复测量方差分析以及事后Tukey检验进行两组和多组之间的比较。对于非正态分布数据，使用Kruskal-Wallis和Mann-Whitney U检验进行组间比较，使用Bonferroni校正进行多重比较。所有检验均为双侧检验，P < 0.05视为具有统计学显著性。无血清培养基促进了人骨髓来源的MSC扩增，并改善了受体小鼠中静脉内施用的MSC的肺植入。SF-MSCs可抑制博莱霉素诱导的肺纤维化过程中血清转化生长因子-β1的降低和血清及支气管肺泡灌洗液中白细胞介素-6的升高。与S-MSC给药相比，SF-MSC给药更强烈地增加了血液和肺中调节性T细胞（Tcells）的数量。此外，SF-MSC表现出对博来霉素诱导的肺纤维化的增强的抗纤维化作用，其通过抗体介导的Treg耗竭而减弱。SF-MSC通过增强Tcl 3进入肺的诱导作用显著抑制BLM诱导的肺炎症和纤维化，并纠正失调的细胞因子平衡。因此，SF-MSCs可能是一个有用的工具，用于防止肺纤维化的进展，没有血清使用的缺点。在线版本包含补充材料，可通过10.1186/s13287-021-02574-5获得。
Mesenchymal stromal cells (MSCs) are a potential therapeutic tool for pulmonary fibrosis. However, ex vivo MSC expansion using serum poses risks of harmful immune responses or unknown pathogen infections in the recipients. Therefore, MSCs cultured in serum-free media (SF-MSCs) are ideal for clinical settings; however, their efficacy in pulmonary fibrosis is unknown. Here, we investigated the effects of SF-MSCs on bleomycin-induced pulmonary inflammation and fibrosis compared to those of MSCs cultured in serum-containing media (S-MSCs). SF-MSCs and S-MSCs were characterized in vitro using RNA sequence analysis. The in vivo kinetics and efficacy of SF-MSC therapy were investigated using a murine model of bleomycin-induced pulmonary fibrosis. For normally distributed data, Student’s t test and one-way repeated measures analysis of variance followed by post hoc Tukey’s test were used for comparison between two groups and multiple groups, respectively. For non-normally distributed data, Kruskal–Wallis and Mann–Whitney U tests were used for comparison between groups, using e Bonferroni’s correction for multiple comparisons. All tests were two-sided, and P < 0.05 was considered statistically significant. Serum-free media promoted human bone marrow-derived MSC expansion and improved lung engraftment of intravenously administered MSCs in recipient mice. SF-MSCs inhibited the reduction in serum transforming growth factor-β1 and the increase of interleukin-6 in both the serum and the bronchoalveolar lavage fluid during bleomycin-induced pulmonary fibrosis. SF-MSC administration increased the numbers of regulatory T cells (Tregs) in the blood and lungs more strongly than in S-MSC administration. Furthermore, SF-MSCs demonstrated enhanced antifibrotic effects on bleomycin-induced pulmonary fibrosis, which were diminished by antibody-mediated Treg depletion. SF-MSCs significantly suppressed BLM-induced pulmonary inflammation and fibrosis through enhanced induction of Tregs into the lungs and corrected the dysregulated cytokine balance. Therefore, SF-MSCs could be a useful tool for preventing pulmonary fibrosis progression without the demerits of serum use. The online version contains supplementary material available at 10.1186/s13287-021-02574-5.
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影响因子：
5.8
作者：
Kobayashi T;Tanaka K;Fujita T;Umezawa H;Amano H;Yoshioka K;Naito Y;Hatano M;Kimura S;Tatsumi K;Kasuya Y
通讯作者：
Kasuya Y
影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
5.5
作者：
Halter, Sebastien;Aimade, Lucrece;Monsel, Antoine
通讯作者：
Monsel, Antoine
DOI：
10.1186/1478-811x-9-12
发表时间：
2011-05-14
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Hass R;Kasper C;Böhm S;Jacobs R
通讯作者：
Jacobs R
DOI：
10.1165/rcmb.2017-0096st
发表时间：
2017-05-01
影响因子：
6.4
作者：
Jenkins, R. Gisli;Moore, Bethany B.;White, Eric S.
通讯作者：
White, Eric S.