By Romeo Alex Penheiro, Riasat Ahmed, Salwa Hasan, Janice Siu Yan Hui, Michael (Jungmin) Son, Sara Chung
















Introduction
Stem cell therapy in neuroscience is not only a fascinating area of research, but it further caters to the need for alternative therapies in nervous system disorders. By definition, stem cells have the capacity for self-renewal (i.e. they divide indefinitely) and they are pluripotent (i.e. they have the capacity to differentiate into many different types of body tissue, including nervous system cells). There are two main types of stem cells: human embryonic stem cells, which are derived from the inner cell mass of a blastocyst, and adult stem cells, which are derived from various mature tissues such as human bone-marrow derived mesenchymal stem cells. Stem cell therapy is particularly relevant for central nervous system disorders, owing to the fact that the central nervous system has very limited capacity for self-repair. Stem cells, as a source of cells, could potentially provide necessary compensation for degeneration of neurons in various parts of the nervous system and/or ameliorate nervous system damage through secondary mechanisms such as providing trophic support to the damaged cells or reducing inflammation[1]. A lot of the diseases/disorders for which stem cell treatments are being investigated do not currently have established treatments, for example, both Huntington’s disease and spinal cord injuries are still being treated symptomatically. Therefore, there is a crucial need to find appropriate treatment mechanisms for these disorders and stem cells have, thus far, shown a lot of positive results in both the laboratory and clinical settings[2]. Currently, research into stem cell treatments is on-going for various degenerative diseases such as multiple sclerosis, Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, as well as for ischemic strokes and spinal cord injuries.

Multiple Sclerosis

1) Introduction
1.1) What is Multiple Sclerosis?
1.2) Causes of Multiple Sclerosis
2) Epidemiology and Current Therapeutics
2.1) Epidemiology
2.2) Current Therapeutics
3) Research Directions - Stem Cells
3.1) Mesenchymal Stem Cells
4) Development of a Clinical Model
4.1) Animal Models
4.2) Human trials
5) Conclusion

Alzheimer’s Disease

1.0 Neural stem cell transplantation
Cell replacement of neural stem cell-derived cholinergic neurons
Brain-derived neurotrophic factor-mediated cognitive improvement
Proton magnetic resonance spectroscopy for quantitative analysis of therapeutic effect of NSC transplantation
1.1 Controlled generation of functional basal forebrain cholinergic neurons
1.2 Neural precursor cell/neural progenitor cell transplantation
Neural progenitor cells attenuate inflammatory reactivity/neuronal loss
Focal neural precursor cell implantation results in glial cell differentiation leading to recovery of cortical neurons
1.3 Mesenchymal stem cell transplantation
Efficient processing of β-amyloid by neuroectodermally converted mesenchymal stem cell
Bone marrow-derived mesenchymal stem cell transplantation reduces β-amyloid deposition and recovers memory deficits
Soluble intracellular adhesion molecule-1 secreted by human umbilical cord blood-derived mesenchymal stem cell reduces β-amyloid plaques


Stem cell therapy for Huntington's disease

a. Use of different stem cells for HD therapy
b. Animal models of HD
c. Induced pluripotent stem cells in human HD cell model
d. Transforming Growth Factors-Beta (TGF-beta) signalling in the brain

Stem Cell Therapy for Parkinson's disease

a. Experimental Approaches
b. Factors affecting the impact of transplanted cells on behavior
c. Four Stages of clinical trials



Stroke

a. Origins and potential of stem cell therapies
b. Stem cell therapy in animal models of stroke
c. Development of therapy for stroke patients
d. Stem cell therapy in current human studies

Spinal Cord Injury

a. Human embryonic stem cells used in rat models of SCI
b. Neural precursor cells reduce secondary tissue damage
c. Olfactory ensheathing cell transplantation
d. Bone marrow derived MSCs promoted functional recovery
e. Therapeutic potential of induced pluripotent stem cells in SCI

References


[1] Cusimano M et al. Transplanted neural stem/precursor cells instruct phagocytes and reduce secondary tissue damage in the injured spinal cord. Brain. (2012) Jan 23 – Epub.
[2] Miller RH and Baj L. Translating stem cell therapies to the clinic. Neuroscience Letters. (2012) Jan 25 – Epub.

Four Stages of Clinical Trials

5. Stroke