The development of new cell replacement strategies using neural stem cells (NSC) may provide an alternative and unlimited cell source for clinical neural
transplantation in
neurodegenerative diseases such as Parkinson's and
Huntington's disease. The clinical application of neural
transplantation using NSC will therefore depend upon the availability of clinical grade NSC that are generated in unlimited quantities in a standardized manner. In order to investigate the utility of NSC in clinical neural
transplantation, undifferentiated murine NSC were first expanded for an extended period of time in
suspension bioreactors containing a serum-free medium. Following expansion in
suspension bioreactors, NSC were still able to differentiate in vitro into both astrocytes and neurons after exposure to
brain-derived neurotrophic factor (
BDNF), suggesting that
bioreactor expansion does not alter cell lineage potentiality. Undifferentiated
bioreactor-expanded NSC were then transplanted into the rodent striatum. Immunohistochemical examination revealed undifferentiated
bioreactor-expanded NSC survived
transplantation for up to 8 weeks and expressed the astrocytic immunohistochemical marker
glial fibrillary acidic protein (GFAP), suggesting that the host striatal environment influences NSC cell fate upon
transplantation. Moreover, no
tumor formation was observed within the graft site, indicating that NSC expanded in
suspension bioreactors for an extended period of time are a safe source of tissue for
transplantation. Future studies should focus on predifferentiating NSC towards specific neuronal phenotypes prior to
transplantation in order to restore behavioral function in rodent models of
neurodegenerative disease.