Cusulin C, Aztiria E, Cacci E, Battaglini PP, Kokaia Z, Leanza G (2007) Survival, integration and differentiation of human neural stem cells transplanted into an animal model of cholinergic degeneration. Neuroscience 2007 Abstracts 779.5/E7. Society for Neuroscience, San Diego, CA.
Summary: The recently characterized F7B cell line, derived from human fetal cortex (Cacci et al, 2007) has been observed able to differentiate in vitro into different glial and neuronal subtypes. However, no much data is available about its capacity for differentiation in vivo. In the present work, F7B cells were grafted to the medial septum of newborn (P8) intact rats and to littermates that had been subjected to selective cholinergic deafferentation at P4 using the 192 IgG-saporin immunotoxin. The animals were sacrificed 1 or 3 months after grafting and the dissected brains were processed for immunocytochemistry, using cell-specific (HuNu and GFP) and differentiation markers (Dcx, GFAP, NeuN, and HuD). Overall, grafted F7B cells exhibited an excellent ability to survive and differentiate into the host tissue environment. Survival rate varied among the groups, being consistently higher when the cells were grafted into lesioned, as opposed to intact, animal. Moreover, a better survival was seen at 1 month, compared to 3 months post-grafting, regardless the lesion condition. Interestingly, the presence of a cholinergic depletion in the recipient appeared to affect differentiation of grafted F7B cells. In fact, higher numbers of Dcx+ and HuD+ cells were scattered within the grafts placed in lesioned animals, as compared to controls. In lesioned, but not intact animals, at 3 months post-grafting, sparse F7B cells were found to express the mature neuronal marker NeuN. On the other hand, grafted F7B immunoreactive for GFAP were similarly detected in all transplanted animals. F7B cells appear to be feasible for transplantation, being able to survive and differentiate into a developing brain, and to positively respond to the new environment created by a lesion. Further studies are warranted to test their actual capacity for functional integration.
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