Serial in vivo imaging of transplanted allogeneic neural stem cell survival in a mouse model of amyotrophic lateral sclerosis.

Abstract Neural stem cells (NSCs) are being investigated as a possible treatment for amyotrophic lateral sclerosis (ALS) through intraspinal transplantation, but no longitudinal imaging studies exist that describe the survival of engrafted cells over time. Allogeneic firefly luciferase-expressing murine NSCs (Luc + -NSCs) were transplanted bilaterally (100,000 cells/2 μl) into the cervical spinal cord (C5) parenchyma of pre-symptomatic (63 day-old) SOD1 G93A ALS mice (n = 14) and wild-type age-matched littermates (n = 14). Six control SOD1 G93A ALS mice were injected with saline. Mice were immunosuppressed using a combination of tacrolimus + sirolimus (1 mg/kg each, i.p.) daily. Compared to saline-injected SOD1 G93A ALS control mice, a transient improvement (p  G93A ALS mice at the time of disease onset (71.7 ± 17.9% at 4 weeks post-transplantation, p  G93A ALS mice, poor cell survival was accompanied by accumulation of mature macrophages and the presence of astrogliosis and microgliosis. We conclude that the disease progression adversely affects the survival of engrafted murine Luc + -NSCs in SOD1 G93A ALS mice as a result of the hostile ALS spinal cord microenvironment, further emphasizing the challenges that face successful cell therapy of ALS.