title: Wnt3a, a Protein Secreted by Mesenchymal Stem Cells Is Neuroprotective and Promotes Neurocognitive Recovery Following Traumatic Brain Injury.
abstract: Intravenous administration of bone marrow derived mesenchymal stem cells (MSCs) has been shown to reduce blood brain barrier compromise and improve neurocognition following traumatic brain injury (TBI). These effects occur in the absence of engraftment and differentiation of these cells in the injured brain. Recent studies have shown that soluble factors produced by MSCs mediate a number of the therapeutic effects. In this study, we sought to determine if intravenous administration of MSCs (IV-MSCs) could enhance hippocampal neurogenesis following TBI. Our results demonstrate that IV-MSC treatment attenuates loss of neural stem cells and promotes hippocampal neurogenesis in TBI injured mice. As Wnt signaling has been implicated in neurogenesis, we measured circulating Wnt3a levels in serum following IV-MSC administration and found a significant increase in Wnt3a. Concurrent with this increase, we detected increased activation of the Wnt/β-catenin signaling pathway in hippocampal neurons. Furthermore, IV recombinant Wnt3a treatment provided neuroprotection, promoted neurogenesis, and improved neurocognitive function in TBI injured mice. Taken together, our results demonstrate a role for Wnt3a in the therapeutic potential of MSCs and identify Wnt3a as a potential stand-alone therapy or as part of a combination therapeutic strategy for the treatment of TBI. Stem Cells 2016;34:1263-1272.
authors: Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
authors: Yuhai
authors: Y
authors: Zhao
authors: Blood Systems Research Institute, San Francisco, California, USA.|Department of Laboratory Medicine, University of California San Francisco, California, USA.
authors: Stuart L
authors: SL
authors: Gibb
authors: Department of Neurobiology and Anatomy, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors: Jing
authors: J
authors: Zhao
authors: Department of Neurobiology and Anatomy, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors: Anthony N
authors: AN
authors: Moore
authors: Department of Neurobiology and Anatomy, University of Texas Health Science Center at Houston, Houston, Texas, USA.|Department of Psychology, Southern Illinois University, Carbondale, Illinois, USA.
authors: Michael J
authors: MJ
authors: Hylin
authors: Blood Systems Research Institute, San Francisco, California, USA.
authors: Tyler
authors: T
authors: Menge
authors: Department of Surgery and Center for Translational Injury Research, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors: Hasen
authors: H
authors: Xue
authors: Blood Systems Research Institute, San Francisco, California, USA.|Department of Laboratory Medicine, University of California San Francisco, California, USA.
authors: Gyulnar
authors: G
authors: Baimukanova
authors: Blood Systems Research Institute, San Francisco, California, USA.|Department of Laboratory Medicine, University of California San Francisco, California, USA.
authors: Daniel
authors: D
authors: Potter
authors: Department of Surgery and Center for Translational Injury Research, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors: Evan M
authors: EM
authors: Johnson
authors: Department of Surgery and Center for Translational Injury Research, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors: John B
authors: JB
authors: Holcomb
authors: Department of Pediatric Surgery, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors: Charles S
authors: CS
authors: Cox
authors: Blood Systems Research Institute, San Francisco, California, USA.
authors: Pramod K
authors: PK
authors: Dash
authors: Department of Surgery and Center for Translational Injury Research, University of Texas Health Science Center at Houston, Houston, Texas, USA.|Department of Psychology, Southern Illinois University, Carbondale, Illinois, USA.
authors: Shibani
authors: S
authors: Pati
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D000070642:Brain Injuries, Traumatic / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002470:Cell Survival / Q000187:drug effects; D003071:Cognition / Q000187:drug effects; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008168:Lung / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D058953:Neural Stem Cells / Q000187:drug effects / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D020127:Recovery of Function / Q000187:drug effects; D016896:Treatment Outcome; D060449:Wnt Signaling Pathway / Q000187:drug effects; D060509:Wnt3A Protein / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D018696:Neuroprotective Agents; D060509:Wnt3A Protein
keywords: Mesenchymal stem cells; Neurogenesis; Neuroprotection; Traumatic brain injury; Wnt3a