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Stem Cells Dev. 2017 Feb 15;26(4):239-248. doi: 10.1089/scd.2016.0108. Epub 2016 Dec 16.

Wharton's Jelly Mesenchymal Stem Cells Protect the Immature Brain in Rats and Modulate Cell Fate.

Author information

1
1 Department of Clinical Research, University of Bern , Bern, Switzerland .
2
2 Department of Obstetrics and Gynecology, University of Bern , Bern, Switzerland .
3
3 Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine , New Haven, Connecticut.
4
4 Society for the Investigation of Early Pregnancy and BioIncept LLC , Cherry Hill, New Jersey.
5
5 Department of Pediatrics, Maastricht University Medical Center (MUMC) , Maastricht, the Netherlands .
6
6 Division Neuroscience, Department of Neuropsychology, School of Mental Health and Neuroscience (MHeNS), Maastricht University , Maastricht, the Netherlands .

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.

KEYWORDS:

WJ-MSCs; cell fate; neuroprotection

PMID:
27842457
DOI:
10.1089/scd.2016.0108
[Indexed for MEDLINE]
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