The basal forebrain cholinergic system is the population of neurons most affected by the neurodegenerative process

- In the last few years, hopes were raised that cell replacement therapy would provide cure by compensating the lost neuronal systems

- Zhang et al. (2013) hypothesized that transplantation of NSC into the hippocampal regions of APP1PS1 transgenic (Tg) mice, a well-established model of AD, would enhance the expression of synaptic proteins, which may be helpful for improving cognitive function

Their results showed that NSC transplantation significantly improved spatial learning and memory function in Tg mice, a well-established model of AD, would enhance the expression of synaptic proteins, which may be helpful for improving cognitive function

The results obtained by real-time RT-PCR, immunofluorescence, and Western blot analyses demonstrated that the expression of synaptophysin (SYN) and that of growth-associated protein-43 (GAP-43) in Tg-NSC mice, 8 weeks after transplantation, were significantly improved compared with what was observed in Tg-Veh (control) mice. o This finding was confirmed by the increase in the number of synapses in Tg-NSC mice as observed via electron microscopy

o Their results suggest that NSC-induced changes can recover memory loss in APP1PS1 transgenic mice, possibly by establishing new neural circuits resulting from the engrafted NSC

Previous studies have shown the preservation of host neurons and recovery of function through the transplantation of human NSCs ex- pressing diverse functional genes, especially growth factors, in animal models of PD, ALS, stroke and spinal cord injury

Due to their high survival rate and ability to differentiate into both neurons and glial cells following transplantation into damaged tissue

Finding an unlimited source of transplantable cells would be a welcome advance in cell therapy. In this regard, stem cell's infinite ability to self-renew and differentiate into neurons makes the search for cell therapy crucial to the next step of clinical application

- As a growth factor secretory cell, human HB1.F3 NSCs have been investigated as graft source for PD

Transplantation of HB1.F3 cells into the striatum of rats with dopamine-depleted nigrostriatal pathway produced by the neurotoxin 6-OHDA significantly ameliorated parkinsonian behavioural symptoms compared with controls via neurotrophic factor secretion among other neurorestorative processes

Park et al., 2012 extended the use of HB1.F3 cells to AD by over-expressing human choline acetyltransferase (ChAT) gene in this NSC line

Using a neurotoxin rat AD model in which ethylcholine mustard aziridinium ion (AF64A) was intracerebroventricularly into the animal's brain, widespread cholinergic neuronal loss was detected and accompanied by memory deficits, resembling many of the salient features of AD

In contrast, transplantation of HB1.F3.ChAT NSCs into the AF64A-lesioned rats led to recovery of the learning and memory function, and induced elevated levels of acetylcholine (ACh) in cerebrospinal fluid (CSF)

Upon further investigation, the migration of the transplanted F3.ChAT human NSCs was traced to various regions of the brain including the cerebral cortex, hippocampus, striatum and septum; these cells were seen to differentiate into neurons and astrocytes