PMID- 29500491 OWN - NLM STAT- MEDLINE DCOM- 20190708 LR - 20190708 IS - 1432-0878 (Electronic) IS - 0302-766X (Linking) VI - 373 IP - 2 DP - 2018 Aug TI - Overexpression of FOXQ1 enhances anti-senescence and migration effects of human umbilical cord mesenchymal stem cells in vitro and in vivo. PG - 379-393 LID - 10.1007/s00441-018-2815-0 [doi] AB - 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. FAU - Zhang, Tao AU - Zhang T AD - School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, China. FAU - Wang, Pan AU - Wang P AD - The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China. FAU - Liu, Yanxia AU - Liu Y AD - School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, China. FAU - Zhou, Jiankang AU - Zhou J AD - School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, China. FAU - Shi, Zhenqing AU - Shi Z AD - School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, China. FAU - Cheng, Kang AU - Cheng K AD - School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, China. FAU - Huang, Tuanjie AU - Huang T AD - School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, China. FAU - Wang, Xinxin AU - Wang X AD - The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China. FAU - Yang, Greta Luyuan AU - Yang GL AD - Stuyvesant High School, New York, NY, 10282, USA. FAU - Yang, Bo AU - Yang B AD - The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China. FAU - Ma, Shanshan AU - Ma S AD - School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, China. mashanshan84@163.com. FAU - Guan, Fangxia AU - Guan F AD - School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, China. guanfangxia@126.com. AD - The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China. guanfangxia@126.com. LA - eng GR - 17A310012/The Key Research Project of Higher Education of Henan Province/ GR - 154200510008/The Plan for Scientific Innovation Talent of Henan Province/ GR - 2016GH15/The International Collaboration Research Program for Talents of Henan Province/ GR - 20114101110004/Research Fund for the Doctoral Program of Higher Education of China/ GR - 15IRTSTHN022/Innovative Research Team in Science and Technology of the University of Henan Province/ GR - 2015M572122/China Postdoctoral Science Foundation/ GR - 81501200/National Natural Science Foundation of China/ PT - Journal Article DEP - 20180303 PL - Germany TA - Cell Tissue Res JT - Cell and tissue research JID - 0417625 RN - 0 (FOXQ1 protein, human) RN - 0 (Forkhead Transcription Factors) SB - IM MH - Alzheimer Disease/metabolism/pathology MH - Animals MH - Cell Differentiation/genetics MH - Cell Movement/*genetics MH - Cell Proliferation/genetics MH - Cellular Senescence/*genetics MH - Disease Models, Animal MH - Forkhead Transcription Factors/genetics/*metabolism MH - HEK293 Cells MH - Humans MH - Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/cytology/*metabolism MH - Mice, Transgenic MH - Umbilical Cord/*cytology OTO - NOTNLM OT - Anti-senescence OT - FOXQ1 OT - Human umbilical cord mesenchymal stem cells OT - Migration OT - Overexpression EDAT- 2018/03/04 06:00 MHDA- 2019/07/10 06:00 CRDT- 2018/03/04 06:00 PHST- 2017/08/13 00:00 [received] PHST- 2018/01/30 00:00 [accepted] PHST- 2018/03/04 06:00 [pubmed] PHST- 2019/07/10 06:00 [medline] PHST- 2018/03/04 06:00 [entrez] AID - 10.1007/s00441-018-2815-0 [pii] AID - 10.1007/s00441-018-2815-0 [doi] PST - ppublish SO - Cell Tissue Res. 2018 Aug;373(2):379-393. doi: 10.1007/s00441-018-2815-0. Epub 2018 Mar 3.