三维微环境手性特征调控间充质干细胞线粒体功能

doi:10.3969/j.issn.1006-7795.2022.03.018

首都医科大学学报 ›› 2022, Vol. 43 ›› Issue (3): 440-445.doi: 10.3969/j.issn.1006-7795.2022.03.018

三维微环境手性特征调控间充质干细胞线粒体功能

何颖¹, 冯传良², 刘进营³, 郑慧敏¹, 江圣杰^1*

1.北京大学口腔医院特诊科, 北京 100034;
2.上海交通大学材料科学与工程学院, 上海 200030;
3.河南大学材料学院特种功能实验室, 郑州 450001

收稿日期:2022-01-27 出版日期:2022-06-21 发布日期:2022-06-01
基金资助:
国家自然科学基金(51833006, 82101072,52003072)。

Chirality controls mitochondrial function of mesenchymal stem cells in three-dimensional microenvironment

He Ying¹ , Feng Chuanliang², Liu Jinying³, Zheng Huiming¹, Jiang Shengjie^1*

1. Department of Geriatric Dentistry,Peking University School and Hospital of Stomatology, Beijing 100034, China;
2. State Key Laboratory of Metal Matrix Composites School of Materials Science and Engineering, Shanghai Jiaotong University, Shanghai 200030, China;
3. Key Laboratory for Special Functional Materials of Ministry of Education School of Materials Science and Engineering, Henan University, Zhengzhou 450001, China

Received:2022-01-27 Online:2022-06-21 Published:2022-06-01
Contact: *E-mail:277062365@qq.com
Supported by:
National Natural Science Foundation of China(51833006, 82101072, 52003072).

摘要/Abstract

摘要： 目的解析手性微环境介导线粒体功能调控骨髓间充质干细胞成骨分化。方法体外通过三维手性微环境培养间充质干细胞监测干细胞的线粒体膜电位功能,在体内观察凝胶植入后早期缺损区域关键调控线粒体功能趋化CXCL2因子的表达,体外高通量组学分析相关线粒体与代谢信号通路的差异。结果免疫荧光染色显示右旋手性基质中线粒体线粒体深红色荧光探针染色比例降低,表明右旋手性基质中的干细胞线粒体膜电位出现损伤。大鼠颅骨缺损模型发现在早期植入三维手性凝胶后左旋组修复区域的CXCL2明显表达上调。京都基因和基因组数据库(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析发现线粒体相关基因与多个信号通路发生了明显的差异表达。差异基因分析发现右旋组中间充质干细胞出现了线粒体降解相关基因的表达上调。左旋手性基质能上调干细胞线粒体NADH脱氢酶活性,右旋手性基质中间充质干细胞线粒体功能出现明显功能损伤。结论生物植入材料基质手性具备调控干细胞线粒体功能能力。

关键词: 手性, 线粒体, 间充质干细胞

Abstract: Objective To analyze the chirality mediated mitochondrial function of stem cells and regulation of osteogenic differentiation. Methods Mesenchymal stem cells (MSCs) were cultured in vitro to monitor the mitochondrial membrane potential function of stem cells in vitro. In vivo, the expression of CXCL2 factor was observed in the early defect area after hydrogel implantation, and the difference between the related mitochondria and metabolic signaling pathways was analyzed by high throughput analysis in vitro. Results The proportion of mitotracker deep red immunoflourence staining decreased in the righ-handed group, which indicated that the mitochondrial membrane potential of stem cells was damaged in the right-handed group. In the rat cranial defects model, the expression of CXCL2 in the left-handed matrix repair area was up-regulated after early implantation. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis found that mitochondrial related genes and signaling pathways were significantly differentially between different chiral groups. A global microarray gene analysis showed that the expression of mitochondrion degradation related genes up-regulated in right-handed group. The results showed that left-handed matrix could up regulate the mitochondrial NADH dehydrogenase expression, while the mitochondrial function of mesenchymal stem cells in right-handed matrix was significantly damaged. Conclusion The chirallity of biological implant materials was able to regulate the function of stem cell mitochondria.

Key words: chirality, mitochondrion, mesenchymal stem cells

中图分类号:

Q731

何颖, 冯传良, 刘进营, 郑慧敏, 江圣杰. 三维微环境手性特征调控间充质干细胞线粒体功能[J]. 首都医科大学学报, 2022, 43(3): 440-445.

He Ying , Feng Chuanliang, Liu Jinying, Zheng Huiming, Jiang Shengjie. Chirality controls mitochondrial function of mesenchymal stem cells in three-dimensional microenvironment[J]. Journal of Capital Medical University, 2022, 43(3): 440-445.

参考文献

[1] Engler A J, Sen S, Sweeney H L, et al. Matrix elasticity directs stem cell lineage specification[J]. Cell, 2006, 126(4): 677-689.
[2] Harada M, Karakawa S, Miyano H, et al. Simultaneous analysis of D,L-amino acids in human urine using a chirality-switchable biaryl axial tag and liquid chromatography electrospray ionization tandem mass spectrometry[J]. Symmetry, 2020, 12(6): 913.
[3] Wei Y, Jiang S J, Si M T, et al. Chirality controls mesenchymal stem cell lineage diversification through mechanoresponses[J]. Adv Mater, 2019, 31(16): e1900582.
[4] Jiang S J, Zeng Q, Zhao K, et al. Chirality bias tissue homeostasis by manipulating immunological response[J]. Adv Mater, 2022, 34(2): e2105136.
[5] 李园琦, 林海, 罗红蓉, 等. 线粒体自噬与骨髓间充质干细胞成软骨分化的关联[J]. 中国组织工程研究, 2020, 24(31): 4954-4960.
[6] Cossu G, Birchall M, Brown T, et al. Lancet commission: stem cells and regenerative medicine[J]. Lancet, 2018, 391(10123): 883-910.
[7] He P, Williams B A, Trout D, et al. The changing mouse embryo transcriptome at whole tissue and single-cell resolution[J]. Nature, 2020, 583(7818): 760-767.
[8] Killaars A R, Grim J C, Walker C J, et al. Extended exposure to stiff microenvironments leads to persistent chromatin remodeling in human mesenchymal stem cells[J]. Adv Sci, 2019, 6(3): 1801483.
[9] Suzuki M, Sujino T, Chiba S, et al. Host-microbe cross-talk governs amino acid chirality to regulate survival and differentiation of B cells[J]. Sci Adv, 2021, 7(10): eabd6480.
[10] Morganti C, Bonora M, Marchi S, et al. Citrate mediates crosstalk between mitochondria and the nucleus to promote human mesenchymal stem cell in vitro osteogenesis[J]. Cells, 2020, 9(4): 1034.
[11] 曹珈琪, 林文, 丁磊, 等. 线粒体DNA甲基化的研究进展[J]. 中国当代医药, 2020, 27(6): 17-21.
[12] Skok M. Mitochondrial nicotinic acetylcholine receptors: mechanisms of functioning and biological significance[J]. Int J Biochem Cell Biol, 2022, 143: 106138.
[13] Hayakawa K, Esposito E, Wang X H, et al. Transfer of mitochondria from astrocytes to neurons after stroke[J]. Nature, 2016, 535(7613): 551-555.
[14] Roger A J, Muñoz-Gómez S A, Kamikawa R. The origin and diversification of mitochondria[J]. Curr Biol, 2017, 27(21): R1177-R1192.
[15] Hijazi I, Wang E, Orozco M, et al. Peroxisomal support of mitochondrial respiratory efficiency promotes ER stress survival[J]. J Cell Sci, 2022, 135(1): jcs259254.

三维微环境手性特征调控间充质干细胞线粒体功能

Chirality controls mitochondrial function of mesenchymal stem cells in three-dimensional microenvironment

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	王梦迪, 郭弋凡, 庞彦余, 刘羽飞, 赵文景. 保肾通络方含药血清调节线粒体自噬对高糖诱导下足细胞氧化损伤的影响[J]. 首都医科大学学报, 2022, 43(5): 687-693.
[2]	李媛媛, 冯琦琦, 张筱宜, 王玉记, 赵明. 不对称有机催化:化繁为简助力药物研发——2021年诺贝尔化学奖[J]. 首都医科大学学报, 2021, 42(5): 883-887.
[3]	丁锚, 杨楠, 黄语悠, 师文娟, 闫峰, 赵咏梅, 刘克建. 线粒体活性氧自由基抑制剂R(+)-普拉克索对脑缺血再灌注损伤大鼠JAK2-STAT3通路及炎性因子TNF-α的影响[J]. 首都医科大学学报, 2021, 42(2): 232-238.
[4]	崔兴, 钟萍. 我的梦想是做“百年老店”——记首都医科大学三博脑科医院神经外科于春江教授[J]. 首都医科大学学报, 2021, 42(1): 167-169.
[5]	王婉晴, 靳路远. 坚持是成功的基石——范志朋教授[J]. 首都医科大学学报, 2020, 41(5): 752-755.
[6]	程姣姣, 阮祥燕, 杜娟, 谷牧青. 间充质干细胞对人冻融卵巢组织移植后低氧期保护作用的研究进展[J]. 首都医科大学学报, 2020, 41(4): 536-541.
[7]	王明洋, 孙争宇, 张丽, 李雅莉, 李林, 张兰. 山茱萸环烯醚萜苷对脑缺血再灌注大鼠线粒体损伤的影响[J]. 首都医科大学学报, 2020, 41(3): 385-390.
[8]	罗建安, 杨树法, 于秀义, 刘欣, 陈振文. 克氏综合征胎儿脐带间充质干细胞模型的建立[J]. 首都医科大学学报, 2019, 40(6): 868-874.
[9]	赵越, 阮祥燕, 王凤春, 李扬璐, 程姣姣, Alfred O. Mueck. 低氧预处理人脐带间充质干细胞治疗早发性卵巢功能不全小鼠的效果研究[J]. 首都医科大学学报, 2019, 40(4): 566-571.
[10]	王兆佳, 武烨, 刘丹, 王美丽, 隗歆, 刘慧荣. 不同浓度β₁-肾上腺素受体自身抗体对心肌细胞存活影响的差异性[J]. 首都医科大学学报, 2019, 40(3): 402-408.
[11]	周平, 刘程, 王秋石, 朱志清, 曹广明, 刘崇东, 张震宇. 人胎盘间充质干细胞治疗小鼠流产的效果研究[J]. 首都医科大学学报, 2019, 40(3): 434-438.
[12]	辛明蔚, 何军琴, 贾朝霞, 武颖, 张莹, 杨维, 尹晓丹. 温肾养血方提高高龄雌鼠卵母细胞质量和胚胎发育潜能的研究[J]. 首都医科大学学报, 2018, 39(6): 815-820.
[13]	吴林果, 刘丹, 武烨, 马新亮, 刘慧荣. 衰老心肌中热休克因子1的表达与线粒体损伤的关系[J]. 首都医科大学学报, 2018, 39(2): 236-242.
[14]	卢勇泉, 陈敏, 高歌, 段春礼, 鲁玲玲, 杨慧. TRPC3参与α-突触核蛋白引起的线粒体损伤[J]. 首都医科大学学报, 2017, 38(6): 857-862.
[15]	赵春松, 邹海强, 李晓波, 闫晓明, 关云谦, 张愚. CM-DiI标记人骨髓间充质干细胞并检测其移植后产生脑源性神经营养因子的实验研究[J]. 首都医科大学学报, 2017, 38(3): 423-430.