Transcript PS2018_librarymodule - University of Leicester

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
‘Progressive damage or death of neurons
leading to a gradual deterioration of the bodily
functions 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)
Stroke
Pathology
Blockage/interruption of blood flow
Cell death
Symptoms
Vary according to artery affected
Treatment
Prevention of 2nd stroke
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
Parkinson’s Disease
Pathology
Loss of dopamine producing neurones that
project to the substantia nigra
Symptoms
Tremor, stiffness, bradykinesia, postural
instability
Treatment
L-DOPA
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
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*
What are stem cells?
Unique characteristics;
1. Unspecialized
Stem cells have no tissue-specific structures
However, can = specialized cells
2. Self-renewing
Stem cells may replicate many times = proliferation
Differentiation
= process by which stem cells give rise to specialized
cells
Stem Cells - categories
Potency
Produced by
Can result in
Totipotent
Produced from first few
divisions of fertilized egg
Any type of cell
Pluripotent
Descendants of totipotent Any type of cell (apart
cells (4/5 days embryonic from totipotent cells)
development)
Multipotent
Undifferentiated cells
located within
differentiated tissue
Unipotent
Cells related to
location
Specific cell type
Sources of stem cells
• Embryonic Stem Cells (ESC’s)
• Adult Stem Cells (ASC’s)
Embryonic Stem
Cells (ESCs)
•
•
•
•
•
Pluripotent
Abundant
Ethical?
Tumours
Immune rejection
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?
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
Core reading
1.
Bjorklund & Lindvall (2000) Cell replacement therapies for
central nervous system disorders. Nature Neuroscience
3: 537-544.
Core reading
2.
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.
Core reading
3.
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.
Core reading
4.
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.
Core reading
5.
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.
Study guide
1. Discuss the pathology and functional consequences of the
various neurodegenerative disorders in relation to cell loss.
2. Why is cell replacement therapy considered useful following the
various neurodegenerative diseases?
3. Discuss the various sources, and ethical concerns associated
with them, of stem cells?
4. Discuss the evidence for functional improvement following cell
replacement therapy (animal and human studies). What are the
mechanisms underlying any functional improvement?
5. Is the use of cell replacement therapy more justified for treatment
of certain diseases compared to others?
6. What issues remain unresolved in the application of stem cell
therapy to human clinical trials?