Stem+Cell+Therapies+in+Neurodegenerative+Diseases

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

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 = <span style="font-family: 'Arial','sans-serif'; font-size: 16px;"> Cell replacement of neural stem cell-derived cholinergic neurons <span style="font-family: 'Arial','sans-serif'; font-size: 16px;"> Brain-derived neurotrophic factor-mediated cognitive improvement <span style="font-family: 'Arial','sans-serif'; font-size: 16px;"> Proton magnetic resonance spectroscopy for quantitative analysis of therapeutic effect of NSC transplantation <span style="font-family: 'Arial','sans-serif'; font-size: 16px;"> Neural progenitor cells attenuate inflammatory reactivity/neuronal loss <span style="font-family: 'Arial','sans-serif'; font-size: 16px;"> Focal neural precursor cell implantation results in glial cell differentiation leading to recovery of cortical neurons <span style="font-family: 'Arial','sans-serif'; font-size: 16px;"> Efficient processing of β-amyloid by neuroectodermally converted mesenchymal stem cell <span style="font-family: 'Arial','sans-serif'; font-size: 16px;"> Bone marrow-derived mesenchymal stem cell transplantation reduces β-amyloid deposition and recovers memory deficits <span style="font-family: 'Arial','sans-serif'; font-size: 16px;"> Soluble intracellular adhesion molecule-1 secreted by human umbilical cord blood-derived mesenchymal stem cell reduces β-amyloid plaques
 * __<span style="font-family: 'Arial','sans-serif';">1.0 Neural stem cell transplantation __ **
 * __<span style="font-family: 'Arial','sans-serif'; font-size: 16px;">1.1 Controlled generation of functional basal forebrain cholinergic neurons __**
 * __<span style="font-family: 'Arial','sans-serif'; font-size: 16px;">1.2 Neural precursor cell/neural progenitor cell transplantation __**
 * __<span style="font-family: 'Arial','sans-serif'; font-size: 16px;">1.3 Mesenchymal stem cell transplantation __**

=<span style="font-family: Tahoma,Geneva,sans-serif; font-size: 90%;">Stem cell therapy for Huntington's disease = <span style="font-family: Tahoma,Geneva,sans-serif; font-size: 110%;">a. Use of different stem cells for HD therapy <span style="font-family: Tahoma,Geneva,sans-serif; font-size: 110%;">b. Animal models of HD <span style="font-family: Tahoma,Geneva,sans-serif; font-size: 110%;">c. Induced pluripotent stem cells in human HD cell model <span style="font-family: Tahoma,Geneva,sans-serif; font-size: 110%;">d. Transforming Growth Factors-Beta (TGF-beta) signalling in the brain

=<span style="font-family: Tahoma,Geneva,sans-serif; font-size: 90%;">Stem Cell Therapy for Parkinson's disease = <span style="font-family: Tahoma,Geneva,sans-serif; font-size: 110%;">a. Experimental Approaches <span style="font-family: Tahoma,Geneva,sans-serif; font-size: 110%;">b. Factors affecting the impact of transplanted cells on behavior <span style="font-family: Tahoma,Geneva,sans-serif; font-size: 110%;">c. Four Stages of __clinical trials__

=<span style="font-family: Tahoma,Geneva,sans-serif; font-size: 90%;">Stroke = <span style="font-family: Tahoma,Geneva,sans-serif; font-size: 110%;">a. Origins and potential of stem cell therapies <span style="font-family: Tahoma,Geneva,sans-serif; font-size: 110%;">b. Stem cell therapy in animal models of stroke <span style="font-family: Tahoma,Geneva,sans-serif; font-size: 110%;">c. Development of therapy for stroke patients <span style="font-family: Tahoma,Geneva,sans-serif; font-size: 110%;">d. Stem cell therapy in current human studies

=<span style="font-family: Tahoma,Geneva,sans-serif; font-size: 90%;">Spinal Cord Injury = <span style="font-family: Tahoma,Geneva,sans-serif; font-size: 110%;">a. Human embryonic stem cells used in rat models of SCI <span style="font-family: Tahoma,Geneva,sans-serif; font-size: 110%;">b. Neural precursor cells reduce secondary tissue damage <span style="font-family: Tahoma,Geneva,sans-serif; font-size: 110%;">c. Olfactory ensheathing cell transplantation <span style="font-family: Tahoma,Geneva,sans-serif; font-size: 110%;">d. Bone marrow derived MSCs promoted functional recovery <span style="font-family: Tahoma,Geneva,sans-serif; font-size: 110%;">e. Therapeutic potential of induced pluripotent stem cells in SCI

=<span style="font-family: Tahoma,Geneva,sans-serif; font-size: 90%;">References =

<span style="font-family: Tahoma,Geneva,sans-serif; font-size: 110%;">[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. <span style="font-family: Tahoma,Geneva,sans-serif; font-size: 110%;">[2] Miller RH and Baj L. Translating stem cell therapies to the clinic. Neuroscience Letters. (2012) Jan 25 – Epub.

<span style="display: block; font-family: Tahoma,Geneva,sans-serif; font-size: 110%; height: 1px; left: -40px; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 648.5px; width: 1px;">Four Stages of __Clinical Trials__

<span style="display: block; font-family: Tahoma,Geneva,sans-serif; font-size: 110%; height: 1px; left: -40px; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 648.5px; width: 1px;">5. Stroke