Making Human Neurons from Stem Cells after Spinal Cord Injury

S pinal cord injury (SCI) has been recognized as one of the conditions for which stem cell transplantation might fi rst prove benefi cial [1]. After SCI, loss of localized myelinating oligodendrocytes and grey matter neurons occurs, with glial scar formation and degeneration of both descending and ascending axons (Figure 1). Replacement of oligodendrocytes to promote remyelination or of neurons to assuage neuronal loss and damage through establishment of relay circuitry or release of trophic factors, are possibilities for stem cell transplantation intervention. Scientists and clinicians recognize the need to move cautiously toward cell replacement goals, as damaging results due to premature clinical testing would be devastating for patients and the emerging stem cell neural repair fi eld. Animal studies need to address fundamental questions—Which is the best cell source for neuron or oligodendrocyte replacement, what is the best location for transplantation, and what is the best time-course after injury? Embryonic stem cells can be pushed to generate cells with characteristics of spinal cord neurons and oligodendrocytes, and studies are ongoing to establish the breadth of spinal cord cell types that can be produced, their long-term stability, and their functional authenticity. Another stem cell source that is being pursued, and that may in fact be closer to the goal of producing a variety of bone fi de spinal cord cells, is stem cells from the spinal cord itself. These are a subclass of neural stem cells (NSCs) and as such are restricted to generating neural tissues, which is a notable advantage over embryonic stem cells, and have the further advantage of being regionally specifi ed to produce spinal cord progeny. Stem cells can be isolated from spinal cord from embryonic through adult stages [2–4]; however, early embryonic stages most readily generate a wide array of spinal cord neurons and glia: NSCs restrict their developmental potency over time, and unfortunately we do not currently know how to reverse the NSC aging process. A recent terrifi c review [5] summarizes the state of stem cell transplantation for SCI. Previous studies on implanting embryonic NSCs after SCI show that these cells can make oligodendrocytes effectively in vivo; however, neuron production is notably poor. These results have led to the idea that the adult SCI environment does not allow NSCs to differentiate effi ciently into neurons. Starting with a more differentiated cell population such as NRPs—restricted progenitors for neurons—allows neuron production [6–8], perhaps because …