title: Wharton's Jelly Mesenchymal Stem Cells Protect the Immature Brain in Rats and Modulate Cell Fate.
abstract: The development of a mammalian brain is a complex and long-lasting process. Not surprisingly, preterm birth is the leading cause of death in newborns and children. Advances in perinatal care reduced mortality, but morbidity still represents a major burden. New therapeutic approaches are thus desperately needed. Given that mesenchymal stem/stromal cells (MSCs) emerged as a promising candidate for cell therapy, we transplanted MSCs derived from the Wharton's Jelly (WJ-MSCs) to reduce the burden of immature brain injury in a murine animal model. WJ-MSCs transplantation resulted in protective activity characterized by reduced myelin loss and astroglial activation. WJ-MSCs improved locomotor behavior as well. To address the underlying mechanisms, we tested the key regulators of responses to DNA-damaging agents, such as cyclic AMP-dependent protein kinase/calcium-dependent protein kinase (PKA/PKC), cyclin-dependent kinase (CDK), ataxia-telangiectasia-mutated/ATM- and Rad3-related (ATM/ATR) substrates, protein kinase B (Akt), and 14-3-3 binding protein partners. We characterized WJ-MSCs using a specific profiler polymerase chain reaction array. We provide evidence that WJ-MSCs target pivotal regulators of the cell fate such as CDK/14-3-3/Akt signaling. We identified leukemia inhibitory factor as a potential candidate of WJ-MSCs' induced modifications as well. We hypothesize that WJ-MSCs may exert adaptive responses depending on the type of injury they are facing, making them prominent candidates for cell therapy in perinatal injuries.
authors.affiliation: 1 Department of Clinical Research, University of Bern , Bern, Switzerland .|2 Department of Obstetrics and Gynecology, University of Bern , Bern, Switzerland .|3 Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine , New Haven, Connecticut.
authors.forename: Martin
authors.initials: M
authors.lastname: Mueller
authors.affiliation: 1 Department of Clinical Research, University of Bern , Bern, Switzerland .|2 Department of Obstetrics and Gynecology, University of Bern , Bern, Switzerland .
authors.forename: Byron
authors.initials: B
authors.lastname: Oppliger
authors.affiliation: 1 Department of Clinical Research, University of Bern , Bern, Switzerland .|2 Department of Obstetrics and Gynecology, University of Bern , Bern, Switzerland .
authors.forename: Marianne
authors.initials: M
authors.lastname: Joerger-Messerli
authors.affiliation: 1 Department of Clinical Research, University of Bern , Bern, Switzerland .|2 Department of Obstetrics and Gynecology, University of Bern , Bern, Switzerland .
authors.forename: Ursula
authors.initials: U
authors.lastname: Reinhart
authors.affiliation: 4 Society for the Investigation of Early Pregnancy and BioIncept LLC , Cherry Hill, New Jersey.
authors.forename: Eytan
authors.initials: E
authors.lastname: Barnea
authors.affiliation: 3 Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine , New Haven, Connecticut.
authors.forename: Michael
authors.initials: M
authors.lastname: Paidas
authors.affiliation: 5 Department of Pediatrics, Maastricht University Medical Center (MUMC) , Maastricht, the Netherlands .|6 Division Neuroscience, Department of Neuropsychology, School of Mental Health and Neuroscience (MHeNS), Maastricht University , Maastricht, the Netherlands .
authors.forename: Boris W
authors.initials: BW
authors.lastname: Kramer
authors.affiliation: 1 Department of Clinical Research, University of Bern , Bern, Switzerland .|2 Department of Obstetrics and Gynecology, University of Bern , Bern, Switzerland .
authors.forename: Daniel V
authors.initials: DV
authors.lastname: Surbek
authors.affiliation: 1 Department of Clinical Research, University of Bern , Bern, Switzerland .|2 Department of Obstetrics and Gynecology, University of Bern , Bern, Switzerland .
authors.forename: Andreina
authors.initials: A
authors.lastname: Schoeberlein
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000473:pathology*; D001930:Brain Injuries / Q000235:genetics / Q000473:pathology / Q000628:therapy; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D009414:Nerve Growth Factors / Q000378:metabolism; D000066829:Neuroprotection / Q000235:genetics; D017208:Rats, Wistar; D015398:Signal Transduction / Q000235:genetics; D059631:Wharton Jelly / Q000166:cytology*
chemical_list: D048948:14-3-3 Proteins; D009414:Nerve Growth Factors
keywords: WJ-MSCs; cell fate; neuroprotection