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 language | English |
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Pages (from-to) | 239-248 |
Number of pages | 10 |
Journal | Stem Cells and Development |
Volume | 26 |
Issue number | 4 |
DOIs | |
Publication status | Published - 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