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PS2018 Biological Psychology

PS2018 Biological Psychology. Section C: Library Module. Topic 3 Stem Cell Therapy for Neurodegenerative Disorders. Dr Claire Gibson School of Psychology, University of Leicester. Neurodegenerative disorders. Neurodegeneration

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PS2018 Biological Psychology

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  1. PS2018 Biological Psychology Section C: Library Module

  2. Topic 3Stem Cell Therapy for Neurodegenerative Disorders Dr Claire Gibson School of Psychology, University of Leicester

  3. Neurodegenerative disorders • Neurodegeneration ‘Progressive damage or death of neurons leading to a gradual deterioration of the bodilyfunctions controlled by the affected part of the nervous system.’ • Acute e.g. stroke • Chronic e.g. Alzheimer’s disease (AD), Parkinson’s Disease (PD), Huntington’s Chorea (HC)

  4. Stroke Pathology Blockage/interruption of blood flow Cell death Symptoms Vary according to artery affected Treatment Prevention of 2nd stroke

  5. Alzheimer’s Disease Pathology Degeneration of hippocampus and cortical tissue Loss of cholinergic neurones Symptoms Progressive memory loss Treatment All aimed at increasing cholinergic action e.g. Aricept

  6. Parkinson’s Disease Pathology Loss of dopamine producing neurones that project to the substantia nigra Symptoms Tremor, stiffness, bradykinesia, postural instability Treatment L-DOPA

  7. Huntington’s Chorea Pathology Loss of GABAergic cells that project from the corpus striatum Symptoms Irregular and involuntary movements dementia, depression Treatment No effective therapy

  8. Neurodegenerative disorders ALL = • extensive cell loss • No (or limited) effective treatments available Cell Replacement Therapy Rationale = replacement of cells lost through disease will improve outcome*

  9. What are stem cells? Unique characteristics; • Unspecialized Stem cells have no tissue-specific structures However, can = specialized cells • Self-renewing Stem cells may replicate many times = proliferation Differentiation = process by which stem cells give rise to specialized cells

  10. Stem Cells - categories

  11. Sources of stem cells • Embryonic Stem Cells (ESC’s) • Adult Stem Cells (ASC’s)

  12. Embryonic Stem Cells (ESCs) • Pluripotent • Abundant • Ethical? • Tumours • Immune rejection

  13. Adult Stem Cells • Undifferentiated cell found amongst differentiated cells of a tissue or organ • Multipotent • Typically generate tissue type from which they reside Examples: liver stem cells, muscle stem cells, nerve stem cells, intestinal stem cells, and hematopoietic (blood-forming) stem cells. • Rare, low in abundance • Plasticity?

  14. Cell Replacement Therapy • Technical stages involved in developing therapies; Proliferate extensively and generate substantial amounts of tissue Differentiate into the desired cell type(s) Survive in the recipient after transplantation Integrate into the surrounding tissue after transplant Function appropriately for duration of recipient’s life Avoid harming recipient in any way

  15. Core reading • Bjorklund & Lindvall (2000) Cell replacement therapies for central nervous system disorders. Nature Neuroscience 3: 537-544.

  16. Core reading • Defer G-L, Geny C, Ricolfi F et al., (1996) Long-term outcome of unilaterally transplanted parkinsonian patients. I. Clinical Approach. Brain 119: 41-50.

  17. Core reading • Lindvall O, Kokaia Z & Martinez-Serrano A (2004) Stem cell therapy for human neurodegenerative disorders – how to make it work? Nature Medicine Volume 10 (July Supplement): S42-S50.

  18. Core reading • Pluchino S, Zanotti L, Deleidi M & Martino G (2005) Neural Stem Cells and their use as a therapeutic tool in neurological disorders. Brain Research Reviews 48: 211-219.

  19. Core reading • Sonntag K-C, Simantov R & Isacson O (2005) Stem cells may reshape the prospect of Parkinson’s disease therapy. Molecular Brain Research 134: 34-51.

  20. Study guide • Discuss the pathology and functional consequences of the various neurodegenerative disorders in relation to cell loss. • Why is cell replacement therapy considered useful following the various neurodegenerative diseases? • Discuss the various sources, and ethical concerns associated with them, of stem cells? • Discuss the evidence for functional improvement following cell replacement therapy (animal and human studies). What are the mechanisms underlying any functional improvement? • Is the use of cell replacement therapy more justified for treatment of certain diseases compared to others? • What issues remain unresolved in the application of stem cell therapy to human clinical trials?

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