In most neurologic conditions, injury to neural cells is followed by an immune response to the damage and consequential neurodegeneration. However, due to different genetic backgrounds, the disease manifestation could be different in each individual. Therefore, it would be ideal to design individualized therapy for each patient suffering the relevant signs and symptoms.
Repairing the central nervous system (CNS) and the reconstruction of the damaged neural network require the removal of etiological factors in the first place, followed by inflammatory response modulation, protection of neural cells from degeneration, and rebuilding the network connections.
In adults, different types of physiological or pathological stimuli can interfere with neurogenesis through changes in the production of new neurons. Various pathological conditions can negatively affect neurogenesis in the brain. These include trauma, infection, malignancy, ischemia, neurodegenerative diseases (such as Alzheimer's disease, Parkinson's, amyotrophic lateral sclerosis and multiple sclerosis) and idiopathic degeneration.
In response to this, stem cells and neural progenitors become activated to increase the proliferation and generation of neurons in the areas surrounding the affected area. However, neural stem cells are not able to induce a complete neurogeneration without the help of some other factors. The ultimate goal would be to rebuild the neural network connections and functional restoration.
Stem cell transplantation has been suggested as an attractive approach to address the limited capacity of the central nervous system for regeneration following acute/chronic injury. Stem cell transplantation can stimulate neural plasticity and restore function.
Recent developments of new techniques have resulted in the possibility of sorting putative NSCs with specific antibodies for cell-specific markers. Also, various methods of cell labeling using genetically tagged NSCs and Y chromosome labeling have been used to track and accurately map NSC traffic in the brain.
Furthermore, two-photon microscopy represents a powerful tool in the analysis of in vivo imaging. Also, functional MRI and electrophysiological measurements have been reported to help in both in vivo and in vitro localization of functional neurons. Electroretinograms have further enabled us to assess the stem cell regenerative capacity in the eye.
One of the properties of NCSs is their migration to home in ischemic and neoplastic areas of brain. Furthermore, three physiological processes, including: reactive astrocytosis, angiogenesis and inflammation induce their migration.
There are many challenges in stem cell therapies in the CNS. Similar to any transplant, there is a possibility for rejection. Also, there is a possibility for cancerogenesis due to excess proliferation. It is a difficult task to recapitulate a part of the adult brain's developmental program.
On the other hand, it would be almost impossible to fully control the microenvironment and its influence in the neuroregeneration. A low cell survival rate has questioned the cell fate of the transplanted cells. Even if the cell survives, the creation of relevant connections in the new location would be difficult to control. Finally, the potential for an immature neuronal excitability would mean network dysfunction with all kinds of unexpected results.
The eagerness of scientists and clinicians has been translated into a large number of premature clinical trials in human patients without the presence of enough of the basic knowledge to elucidate mechanisms of proliferation and cellular identity in the CNS; the mechanism of stem cells being directed into neuronal lineages; potential genetic, pharmacological and behavioral interventions that modulate neurogenic activity; and the CNS regeneration limitations in adults.
The therapeutic potential of stem cells in acute cerebral injury is actively being tested in many clinical trials. However, extensive basic research and more comprehensive, carefully designed trials will be needed in order to achieve an optimal transplantation strategy and personalized approaches for each individual.
