User:MinaMcKee/Neural stem cell

Regenerative Therapy of the CNS
Cell death is a characteristic of acute CNS disorders as well as neurodegenerative disease. The loss of cells is amplified by the lack of regenerative abilities for cell replacement and repair in the CNS. One way to circumvent this is to use cell replacement therapy via regenerative NSCs. NSCs can be cultured in vitro as neurospheres. These neurospheres are composed of neural stem cells and progenitors (NSPCs) with growth factors such as EGF and FGF. The withdrawal of these growth factors activate differentiation into neurons, astrocytes, or oligodendrocytes which can be transplanted within the brain at the site of injury. The benefits of this therapeutic approach have been examined in Parkinson's disease, Huntington's disease, and multiple sclerosis. NSPCs induce neural repair via intrinsic properties of neuroprotection and immunomodulation. Some possible routes of transplantation include intracerebral transplantation and xenotransplantation.

For neurodegenerative diseases, another transplantation therapy arising in research is the directional induction of neural stem cells. '''The direct transplantation of NCSs is limited and faces challenges due to low survival rate and irrational differentiation. To overcome the limitations, the direct induction of NCSs aims to manipulate the differentiation of NCS prior to transplantation. Currently NSCs are obtained from primary CNS tissues, the differentiation of pluripotent stem cells (PSC) and transdifferentiation from somatic cells. Induced NCSs can be reprogrammed from somatic cells. Hence, directional induction takes NSCs from different sources and forces them to differentiate into the desired neural lineage cells. An example of the therapeutic usage of this technique is the targeted differentiation of ventral midbrain dopaminergic (DAergenic) neurons into different models of PD. Current therapies for the neurodegenerative disease Parkinson’s Disease (PD) include dopamine replacement therapy (DRT). This works to alleviate PD symptoms, but as the disease progresses, the alleviating mechanisms are affected in a nonlinear manner.'''

An alternative therapeutic approach to the transplantation of NSPCs is the pharmacological activation of endogenous NSPCs (eNSPCs). Activated eNSPCs produce neurotrophic factors, several treatments that activate a pathway that involves the phosphorylation of STAT3 on the serine residue and subsequent elevation of Hes3 expression (STAT3-Ser/Hes3 Signaling Axis) oppose neuronal death and disease progression in models of neurological disorder.