- Perinatal brain damage
- Stem cell therapy
- Placenta- and unbilical cord-derived stem cells
- Exosomes / extracellular vesicles
- Non-coding RNA & epigenetics
- PreImplantation factor as a novel neuroprotective agent
- Animal model
- Human mesenchymal stem cells
- Stem cell transplantation
- Neural differentiation
Preterm delivery is a major cause of severe neonatal morbidity and mortality: about 1% of newborns are affected by neurological injuries leading to significant learning disabilities, cerebral palsy or mental retardation. Brain lesions observed in newborns later developing cerebral are mainly caused by ischemia due to maturation-dependent reduced cerebral blood flow and maternal/fetal infection and inflammation which are usually present in early preterm delivery. The damage is characterized by the degeneration of the white and grey matter, mostly due to the loss of oligodendrocyte progenitor cells (OPC), followed by myelination disturbances and axonal degeneration. While several potential neuroprotective measures have shown little success in vivo, studies in animal models have suggested that transplantation of stem cells could lead to the regeneration and/or repair of injured neural tissues. Mesenchymal stem cells (MSC) are multipotent cells able to differentiate into mesodermal and neuroectodermal lineages following appropriate stimulation. We isolate MSC from placenta and the Wharton’s jelly of umbilical cords, both ethically acceptable and easily accessible sources of tissue. They may serve as an autologous cell graft for pre- and perinatal neuroregeneration, bypassing immunologic rejection. The cell transplantation as a potential therapy is tested in an animal model of perinatal brain injury.
Exosomes are small vesicles secreted by the cells and contain proteins, lipids, and nucleic acids (e.g. microRNA), which they transfer from cell to cell. The administration of exosomes derived from mesenchymal stem cells was shown to promote neuroregeneration in a variety of disease models. Their cargo, specifically non-coding RNAs (ncRNAs), have gained increasing interest for their regulatory functions in brain development and neurological disorders. Our aim is to characterize the cargo of umbilical cord MSC (WJ-MSC)-derived exosomes with a focus on ncRNAs and to assess the effect of the WJ-MSC exosomes in in vitro and in vivo models of neonatal brain injury.
An additional research focus is the assessment of synthetic preimplantation factor (sPIF) as a novel therapeutic agent for the treatment of neonatal brain injury. PIF is a short peptide produced by the early embryo, modulates maternal immune tolerance and promotes embryo implantation. The synthetic analog (sPIF, BioIncept LLC, proprietary) induces neuroprotection, in part through regulating ncRNAs. Our aim is to better understand the underlaying mechanisms.