Overexpression of FOXQ1 enhances anti-senescence and migration effects of human umbilical cord mesenchymal stem cells in vitro and in vivo
Overexpression of FOXQ1 enhances anti-senescence and migration effects of human umbilical cord mesenchymal stem cells in vitro and in vivo
复制标题
FOXQ1过表达增强人脐带间充质干细胞体内外抗衰老和迁移作用
DOI：
10.1007/s00441-018-2815-0
复制
发表时间：
2018-03
影响因子：
3.6
通讯作者：
Guan Fangxia
中科院分区：
文献类型：
--
作者：
Zhang Tao;Wang Pan;Liu Yanxia;Zhou Jiankang;Shi Zhenqing;Cheng Kang;Huang Tuanjie;Wang Xinxin;Yang Greta Luyuan;Yang Bo;Ma Shanshan;Guan Fangxia
间充质干细胞（Mesenchymal stem cells，MSCs）是一种独特的前体细胞，具有自我更新和分化潜能。这些细胞提供了易于分离和有限的伦理问题作为资源的优势，并代表了一种有前途的神经退行性疾病的细胞疗法。然而，细胞培养过程中的复制性衰老以及移植后细胞迁移和分化的低效率是主要障碍。在我们之前的研究中，我们发现FOXQ 1直接结合SIRT 1启动子来调节细胞衰老，并在许多肿瘤细胞系中促进细胞增殖和迁移。目前，关于FOXQ 1对正常体细胞的影响知之甚少。因此，我们研究FOXQ 1对MSC衰老和迁移的影响。慢病毒载体介导的FOXQ 1在人脐带间充质干细胞（hUC-MSCs）中的过表达导致细胞增殖和活力增强。此外，与衰老正相关的蛋白质和标记物（p16、p21、p53）的表达降低，而与衰老负相关的蛋白质（SIRT 1、PCNA）的表达增加。在阿尔茨海默病动物模型（APPV 717 I转基因小鼠）中移植过表达FOXQ 1的hUC-MSC后，导致阿尔茨海默病（AD）对认知功能和病理性衰老的影响的改善，伴随着AD脑中hUC-MSC数量的增加。总之，FOXQ 1过表达促进hUC-MSCs在体外和体内的抗衰老和迁移。这些发现还表明，这种策略可能有助于优化干细胞治疗的效率。
Mesenchymal stem cells (MSCs) are unique precursor cells characterized by active self-renewal and differentiation potential. These cells offer the advantages of ease of isolation and limited ethical issues as a resource and represent a promising cell therapy for neurodegenerative diseases. However, replicative senescence during cell culture as well as low efficiency of cell migration and differentiation after transplantation are major obstacles. In our previous study, we found that FOXQ1 binds directly to the SIRT1 promoter to regulate cellular senescence and also promotes cell proliferation and migration in many tumor cell lines. Currently, little is known about the effects of FOXQ1 on normal somatic cells. Therefore, we examine the effects of FOXQ1 on senescence and migration of MSCs. Lentiviral vector-mediated overexpression of FOXQ1 in human umbilical cord mesenchymal stem cells (hUC-MSCs) resulted in enhanced cell proliferation and viability. Furthermore, the expression of proteins and markers positively associated with senescence (p16, p21, p53) was reduced, whereas expression of proteins negatively associated with senescence (SIRT1, PCNA) was promoted. Following transplantation of hUC-MSCs overexpressing FOXQ1 in an animal model of Alzheimer’s disease (APPV717I transgenic mice) resulted in amelioration of the effects of Alzheimer’s disease (AD) on cognitive function and pathological senescence accompanied the increased numbers of hUC-MSCs in the AD brain. In conclusion, FOXQ1 overexpression promotes anti-senescence and migration of hUC-MSCs in vitro and in vivo. These findings also suggest that this strategy may contribute to optimization of the efficiency of stem cell therapy.
登录
查看更多内容
影响因子：
--
作者：
B. Rajput;S. Chakrabarti;Vaishali S Dongare;C. Ramirez;K. Deb
通讯作者：
B. Rajput;S. Chakrabarti;Vaishali S Dongare;C. Ramirez;K. Deb
影响因子：
3.7
作者：
Wagner W;Bork S;Horn P;Krunic D;Walenda T;Diehlmann A;Benes V;Blake J;Huber FX;Eckstein V;Boukamp P;Ho AD
通讯作者：
Ho AD
影响因子：
4.6
作者：
Katsuda, Takeshi;Tsuchiya, Reiko;Kosaka, Nobuyoshi;Yoshioka, Yusuke;Takagaki, Kentaro;Oki, Katsuyuki;Takeshita, Fumitaka;Sakai, Yasuyuki;Kuroda, Masahiko;Ochiya, Takahiro
通讯作者：
Ochiya, Takahiro
影响因子：
4.8
作者：
Wang, Qiushi;Yang, Qiaoni;Yuan, Zhengwei
通讯作者：
Yuan, Zhengwei
从人尿液中的细胞生成无整合的神经祖细胞
影响因子：
48
作者：
Wang, Lihui;Wang, Linli;Pei, Duanqing
通讯作者：
Pei, Duanqing