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Transplantation of Mesenchymal Stem Cells Overexpressing Fibroblast Growth Factor 21 Facilitates Cognitive Recovery and Enhances Neurogenesis in a Mouse Model of Traumatic Brain Injury.

التفاصيل البيبلوغرافية
العنوان: Transplantation of Mesenchymal Stem Cells Overexpressing Fibroblast Growth Factor 21 Facilitates Cognitive Recovery and Enhances Neurogenesis in a Mouse Model of Traumatic Brain Injury.
المؤلفون: Shahror RA; Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University and National Health Research Institutes, Taipei, Taiwan.; TMU Neuroscience Research Center, Taipei Medical University, Taipei, Taiwan., Linares GR; Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland.; Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California., Wang Y; Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan., Hsueh SC; Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University and National Health Research Institutes, Taipei, Taiwan.; TMU Neuroscience Research Center, Taipei Medical University, Taipei, Taiwan., Wu CC; TMU Neuroscience Research Center, Taipei Medical University, Taipei, Taiwan.; Department of Neurosurgery, Taipei Medical University Hospital, Taipei, Taiwan.; Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan., Chuang DM; Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University and National Health Research Institutes, Taipei, Taiwan.; Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland., Chiang YH; Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University and National Health Research Institutes, Taipei, Taiwan.; TMU Neuroscience Research Center, Taipei Medical University, Taipei, Taiwan.; Department of Neurosurgery, Taipei Medical University Hospital, Taipei, Taiwan.; Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan., Chen KY; Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University and National Health Research Institutes, Taipei, Taiwan.; TMU Neuroscience Research Center, Taipei Medical University, Taipei, Taiwan.
المصدر: Journal of neurotrauma [J Neurotrauma] 2020 Jan 01; Vol. 37 (1), pp. 14-26. Date of Electronic Publication: 2019 Aug 20.
نوع المنشور: Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Mary Ann Liebert Country of Publication: United States NLM ID: 8811626 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1557-9042 (Electronic) Linking ISSN: 08977151 NLM ISO Abbreviation: J Neurotrauma Subsets: MEDLINE
أسماء مطبوعة: Publication: Larchmont, NY : Mary Ann Liebert
Original Publication: New York, NY : Mary Ann Liebert, c1988-
مواضيع طبية MeSH: Neurogenesis*/physiology , Recovery of Function*, Brain Injuries, Traumatic/*pathology , Fibroblast Growth Factors/*metabolism , Mesenchymal Stem Cell Transplantation/*methods, Animals ; Disease Models, Animal ; Hippocampus/pathology ; Maze Learning ; Memory ; Mice ; Mice, Inbred C57BL
مستخلص: Traumatic brain injury (TBI) is a progressive and complex pathological condition that results in multiple adverse consequences, including impaired learning and memory. Transplantation of mesenchymal stem cells (MSCs) has produced limited benefits in experimental TBI models. Fibroblast growth factor 21 (FGF21) is a novel metabolic regulator that has neuroprotective effects, promotes remyelination, enhances angiogenesis, and elongates astrocytic processes. In this study, MSCs were genetically engineered to overexpress FGF21 in order to improve their efficacy in TBI. MSCs overexpressing FGF21 (MSC-FGF21) were transplanted to mouse brain by intracerebroventricular injection 24 h after TBI was induced by controlled cortical impact (CCI). Hippocampus-dependent spatial learning and memory, assessed by the Morris water maze test, was markedly decreased 3-4 weeks after TBI, a deficit that was robustly recovered by treatment with MSC-FGF21, but not MSC-mCherry control. Hippocampus-independent learning and memory, assessed by the novel object recognition test, was also impaired; these effects were blocked by treatment with both MSC-FGF21 and MSC-mCherry control. FGF21 protein levels in the ipsilateral hippocampus were drastically reduced 4 weeks post-TBI, a loss that was restored by treatment with MSC-FGF21, but not MSC-mCherry. MSC-FGF21 treatment also partially restored TBI-induced deficits in neurogenesis and maturation of immature hippocampal neurons, whereas MSC-mCherry was less effective. Finally, MSC-FGF21 treatment also normalized TBI-induced impairments in dendritic arborization of hippocampal neurons. Taken together, the results indicate that MSC-FGF21 treatment significantly improved TBI-induced spatial memory deficits, impaired hippocampal neurogenesis, and abnormal dendritic morphology. Future clinical investigations using MSC-FGF21 to improve post-TBI outcomes are warranted.
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فهرسة مساهمة: Keywords: fibroblast growth factor 21; mesenchymal stem cells; neurogenesis; spatial learning and memory; traumatic brain injury
المشرفين على المادة: 0 (fibroblast growth factor 21)
62031-54-3 (Fibroblast Growth Factors)
تواريخ الأحداث: Date Created: 20190713 Date Completed: 20210412 Latest Revision: 20210412
رمز التحديث: 20240829
مُعرف محوري في PubMed: PMC6921331
DOI: 10.1089/neu.2019.6422
PMID: 31298621
قاعدة البيانات: MEDLINE
الوصف
تدمد:1557-9042
DOI:10.1089/neu.2019.6422