Stem cells from adult humans develop into neurons in the chicken embryo spinal cord but are they functionally integrated in neural networks?

Neural cell transplantation for repair of CNS lesions is one of the most exciting new avenues in the field of Neuroscience. With regard to spinal cord injuries (SCI), however, neuronal replacement has received relatively little attention because SCI has b een thought to be a "white matter" problem (oligodendrocyte inhibition of axon regrowth). However, recent evidence indicates that loss of gray matter also causes severe motor deficits, suggesting that restoration of the spinal gray matter may also play a n important role in recovery. Regardless of the mode of SCI repair, a crucial question is whether regenerated axons or transplanted cells have the proper synaptic connections to ensure functional recovery. This has hardly been addressed in international r esearch into spinal cord injury. In particular, no studies have used electrophysiological methods to address whether stem cells integrate into spinal neural networks. To address this issue we will use our newly developed xenotypic in vivo model (regenera ting chicken embryo spinal cord) which stimulates human hematopoietic stem cells (hHSCs) to differentiate into neurons. Being the first to employ electrophysiological approaches to show that human stem cell-derived neurons display synaptic activity in viv o (Sigurjonsson et al, 2005), we have now a unique opportunity to maintain a leading position in this field internationally. To determine whether and with what specificity the hHSC-derived neurons functionally integrate into spinal networks, we will analy ze their synaptic connectivity using electrophysiological recording. Specifically, we will assess synaptic inputs from peripheral sensory afferents and from supraspinal descending pathways, both major sources of inputs that control movement. The proposed research will take place in Professor Joel Glover's group at the University of Oslo. The outcome of the proposed research will be particularly important for future use of stem cells in reparative medicine.