Mesenchymal stem cells for the treatment of perinatal brain damage: anti-inflammatory and regenerative effects

• Applicant: Professorin Dr. Ursula Felderhoff-Müser
• Subject Area: Molecular and Cellular Neurology and Neuropathology
• Term: from 2012 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 215554466

Brain injury is a leading cause of perinatal death and neurodevelopmental morbidity in childhood. To date, the only clinically applicable intervention is hypothermia in asphyxiated babies within 6 h following the insult, which improves outcome in some moderately injured term-born infants. Therefore, identification of further neuroprotective and regenerative strategies is highly warranted.In clinically relevant models of perinatal brain injury, we propose to reduce cell death, restore lost tissue and improve functional outcome by transplantation of mesenchymal stem cells (MSC) overexpressing the growth factor BDNF (MSC-BDNF). The Utrecht group has demonstrated that intracerebral transplantation of MSC in a mouse model of asphyxia in term babies significantly improves motor function and reduces lesion size. These encouraging findings require further investigation of the underlying mechanisms, applicability in other clinically relevant models, and further improvement of efficacy by generating MSC-BDNF. We will use a clinically relevant model for term asphyxia (hypoxiaischemia in P9 mice, Utrecht) and a model for brain damage in preterm babies (hyperoxia plus inflammatory challenge in P5 mice, Essen) to address the following questions: 1. Do MSC or MSCBDNF transplantation into the brain alter the inflammatory and growth factor environment and enhance endogenous cell proliferation in the damaged neonatal brain? 2. Does MSC or MSC-BDNF transplantation enhance formation of new neurons and oligodendrocytes, neuronal sprouting and oligodendrocyte maturation? 3. Does MSC or MSC-BDNF transplantation after neonatal brain damage reduce lesion size and improve sensorimotor and cognitive outcome? These data will pave the way to apply MSC transplantation as a treatment regimen for infants suffering of perinatal brain injury.

• DFG Programme: Research Grants
• International Connection: Netherlands
• Participating Persons: Professor Dr. Cobi J. Heijen; Dr. Annemieke Kavelaars; Privatdozent Dr. Matthias Keller