Adult neural stem cells show promise for Huntington's Disease
A new study published in Gene Therapy [(2007) 14. 118-128] links GDNF secreting adult neural stem cells to neuroprotection in a Huntington’s Disease (HD) mouse model.   The original article published by JR Pineda and colleagues this month provides further evidence for the regenerative potential of adult stem cells as surrogate protein pumps in neurodegenerative disorders.  Seminal work by Bjorklund and Lindvall and more recently championed by Svendsen and Kordower has clearly shown a neuroprotective effect of GDNF when supplied by in vivo or ex vivo viral or cell mediated delivery in both Parkinson’s Disease (PD) and HD non-human primate models as well as phase 1 clinical trials.
    The study utilized a murine immortalized neural stem cell line (C17.2), genetically engineered to secrete the neurotrophic factor GDNF, to partially prevent degeneration of striatal neurons and reduce amphetamine-induced rotational behavior in an excitotoxic mouse model of HD.  In addition, the group used optical neuroimaging and co-expressed the firefly luciferase gene with green fluorescent protein (GFP) in the C17.2-GDNF cell line to demonstrate that light photons can be used to effectively quantify the proliferative and migratory capacity of transplantable precursors within the adult CNS, in vivo. 
    This non-intrusive method for tracking exogenous stem cells in vivo will allow for long-term analysis of newly derived cell lines, creating a real-time assay for unwarranted, uncontrolled long-term proliferation. Such proliferative stem cell "tumors" have been reported recently in a study utilizing human embryonic stem cell derived dopaminergic cell transplants in a rat model of PD. Furthermore, at a relative detection limit as low as 500 NSCs within the striata, optical neuroimaging allows for relative quantification of post-transplantation cell survival at various time points throughout the duration of the experiment to establish and monitor the success of the graft as the animal progresses.  Simple monitoring, therefore, leads to direct cost benefits to the investigator by saving time and money lost due to caring for animals that received poor engraftments in large expensive long-term studies.  If this technology evolves into larger animal systems like the non-human primate, it could be an extremely useful tool for the establishment of criteria for successful cellular transplantations including rationale for correct anatomical targeting and cellular density necessary for successful engraftment.

-Dustin R. Wakeman   01/08/07

ARTICLE:  Pineda JR, Rubio N, Akerud P, Urban N, Badimon L, Arenas E, Alberch J, Blanco J, Canals JM. Neuroprotection by GDNF-secreting stem cells in a Huntington's disease model: optical neuroimage tracking of brain-grafted cells. Gene Ther. 2007 Jan;14(2):118-128.  Full Article