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

Martin Mueller*, Byron Oppliger, Marianne Joerger-Messerli, Ursula Reinhart, Eytan Barnea, Michael Paidas, Boris W. Kramer, Daniel V. Surbek, Andreina Schoeberlein

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)239-248
Number of pages10
JournalStem Cells and Development
Volume26
Issue number4
DOIs
Publication statusPublished - 15 Feb 2017

Keywords

  • WJ-MSCs
  • neuroprotection
  • cell fate
  • WHITE-MATTER INJURY
  • NEONATAL ISCHEMIC BRAIN
  • HYPOXIA-ISCHEMIA
  • PRETERM BIRTH
  • PERIVENTRICULAR LEUKOMALACIA
  • CORD BLOOD
  • KINASE-C
  • MODEL
  • THERAPY
  • DAMAGE

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