The objective of this grant is to investigate whether transplantation of human central nervous system stem cells (CNS-SC) can contribute to functional recovery of spinal cord injury (SCI). We created cell banks of human CNS-SC generated from prospective isolated human CNS-SC from fetal brain tissues. We have characterized these cell banks of CNS-SC by transplanting them into the brains of NOD/SCID mice and demonstrated that the human cells engraft, proliferate, migrate and differentiate into neurons, astrocytes and oligodendrocytes in response to host environmental signals. We hypothesize that human CNS-SC may be able respond to SCI and provide trophic factors that induce axon extensions or block the effects of inhibitory substances in the injury site. The graft may also provide cellular support such as intermediary neurons or glial cells to provide a framework through which regenerating axons can traverse the lesion site more effectively. Recently, we have optimized conditions to carry out mouse contusion SCI using NOD/SCID. We propose to transplant human CNS-SC neurosphere cells into proximal sites of spinal cord after contusion injury to NOD-SCID mice. We will evaluate improvement of paralysis by measuring BBB behavior testing and subsequently characterize engraftment, migration and differentiation potential of transplanted human CNS-SC.
| Salazar, Desiree L; Uchida, Nobuko; Hamers, Frank P T et al. (2010) Human neural stem cells differentiate and promote locomotor recovery in an early chronic spinal cord injury NOD-scid mouse model. PLoS One 5:e12272 |
| Hooshmand, Mitra J; Sontag, Christopher J; Uchida, Nobuko et al. (2009) Analysis of host-mediated repair mechanisms after human CNS-stem cell transplantation for spinal cord injury: correlation of engraftment with recovery. PLoS One 4:e5871 |
| Cummings, Brian J; Uchida, Nobuko; Tamaki, Stan J et al. (2006) Human neural stem cell differentiation following transplantation into spinal cord injured mice: association with recovery of locomotor function. Neurol Res 28:474-81 |
| Cummings, Brian J; Uchida, Nobuko; Tamaki, Stanley J et al. (2005) Human neural stem cells differentiate and promote locomotor recovery in spinal cord-injured mice. Proc Natl Acad Sci U S A 102:14069-74 |
