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

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

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.

MeSH terms

  • 14-3-3 Proteins / metabolism
  • Animals
  • Animals, Newborn
  • Brain / pathology*
  • Brain Injuries / genetics
  • Brain Injuries / pathology
  • Brain Injuries / therapy
  • Cell Differentiation / genetics
  • Cell Lineage* / genetics
  • Gene Expression Profiling
  • Humans
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology*
  • Nerve Growth Factors / metabolism
  • Neuroprotection* / genetics
  • Rats, Wistar
  • Signal Transduction / genetics
  • Wharton Jelly / cytology*

Substances

  • 14-3-3 Proteins
  • Nerve Growth Factors