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Glial Progenitor Cell Transplantation in Mice with PVL

Perinatally acquired white matter injury (PWMI), also referred to as Periventricular Leukomalacia (PVL) is the leading cause of neurologic morbidity in premature infants leading to cerebral palsy and other neurocognitive problems affecting more than 50,000 children in the United States every year. PWMI is thought to be due to selective vulnerability of oligodendrocyte progenitor cells, which are predominant in the third trimester and give rise to myelin producing oligodendrocytes. Currently there is no therapy for PWMI. There are anecdotal reports suggesting a beneficial effect of cord blood stem cells in children with cerebral palsy, and recently it has been reported that oligodendrocyte progenitor cells can be derived in-vitro from cord blood cell cultures. In fact multiple private institutions are currently offering ‘stem cell therapy’ without internationally accepted peer-reviewed scientific evidence, and there is a lack of pre-clinical experiments to evaluate the efficacy and safety of these interventions. In this proposal, we plan to conduct transplantation studies of human fetal glial precursor cells and human cord blood stem cells in a new mouse model for PWMI and evaluate the effect of these cells by combining sequential in-vivo MRI studies with histologic techniques. In collaboration with Dr. Michael Johnston, Dr. Susumu Mori, we have recently developed a mouse model for PWMI and we have been able to monitor disease severity by employing advanced in-vivo Magnetic Resonance Imaging (MRI) studies. In a pilot study we have derived mouse glial precursor cells and have further engineered them to express green fluorescent protein. These cells were transplanted into newborn pups with PWMI and we have preliminary data to demonstrate that these transplanted cells are able to survive in the injured brain and migrate along the white matter lesion. 

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