PS2018: Biological Psychology
Library Topic: Stem Cell Therapy for Neurodegenerative Disorders
Library Module: Dr Claire Gibson
Overview
Stem cells are immature cells with prolonged self-renewal capacity and, depending on
their origin, ability to differentiate into multiple cells types or all cells of the body.
Transplantation of stem cells or their derivatives, and mobilisation of endogenous
stem cells within the adult brain, have been proposed as future therapies for
neurodegenerative disorders. All neurodegenerative disorders share a common
pathological feature of extensive cell loss leading to functional abnormalities. Studies
in animal models have demonstrated that neuronal replacement and partial
reconstruction of damaged neuronal circuitry is possible.
Importantly, there is evidence from clinical trials that cell replacement in the diseased
human brain can lead to symptomatic relief. In fact, cell transplants were first carried
out in patients suffering from Parkinson’s disease over 20 years ago. However, as
yet, such treatments have failed to translate into routine therapeutic use and cell
replacement therapy for many neurodegenerative disorders is still at the experimental
stage. It may be considered unrealistic to induce functional recovery by replacing
cells lost through disease, considering the complexity of human brain structure and
function. There is ongoing debate within the scientific community over ethical
concerns regarding the source of stem cells and whether they do actually represent a
realistic therapeutic option for neurodegenerative diseases.
The aim of this module is to demonstrate how cell replacement therapy can lead to
functional recovery of symptoms following neurodegenerative diseases. Where
relevant, evidence from experimental and clinical studies will be discussed. We will
review the current evidence for using stem cells whilst also being aware of the
scientific and ethical concerns. Although a large number of studies have reported the
survival and integration of transplanted cells into neural circuits the focus within this
topic is the behavioural consequences of stem cell therapy.
*Although the term ‘neurodegenerative disorders’ refers to many disorders the focus
within this module is limited to: Parkinson’s disease, Alzheimer’s disease,
Huntington’s chorea, and Stroke.
Core Reading
 Bjorklund A & Lindvall O (2000) Cell replacement therapies for central nervous
system disorders. Nature Neuroscience 3: 537-544.
 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.
 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.
 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.
 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.
Further Reading
These references are recommended reading. They will enable students to gain a wider
appreciation of the topic and go into more depth on different aspects of the topic.
You may wish to search the literature yourself to find other relevant material.
You are not expected to read all these papers in full as generally it is the introduction
and discussion which will be most relevant.
 Bjorklund A, Dunnett SB, Stenevi U, Lewis ME & Iversen SD (1980)
Reinnervation of the denervated striatum by subsantia nigra transplants: functional
consequences as revealed by pharmacological and sensorimotor testing. Brain
Research 199: 307-333.
 Bjorklund A, Dunnet SB, Brundin P et al. (2003) Neural transplantation for the
treatment of Parkinson’s disease. THE LANCET Neurology 2: 437-445.
 Dunnett SB, Bjorklund A, Stenevi U & Iversen SD (1981) Behavioural recovery
following transplantation of substantia nigra in rats subjected to 6-OHDA lesions
of the nigrostriatal pathway. I. Unilateral lesions. Brain Research 215: 147-161.
 Dunnett SB, Bjorklund A, Stenevi U & Iversen SD (1981) Behavioural recovery
following transplantation of substantia nigra in rats subjected to 6-OHDA lesions
of the nigrostriatal pathway. II. Bilateral lesions. Brain Research 229: 457-470.
 Dunnett SB, Bjorklund & Lindvall O (2001) Cell therapy in Parkinson’s disease –
stop or go? Nature Reviews Neuroscience 2: 365-369.
 Isacson O (2003) The production and use of cells as therapeutic agents in
neurodegenerative diseases. THE LANCET Neurology 2: 417-424.
 Lee S-T, Chu K, Park J-E et al. (2005) Intravenous administration of human neural
stem cells induces functional recovery in Huntington’s disease rat model.
Neuroscience Research 52: 243-249.
 Lindvall O, Brundin P, Widner H et al. (1990) Grafts of fetal dopaminergic
neurons survive and improve motor function in Parkinson’s disease. Science 247:
574-578.
 Lindvall O & Kokaia A (2004) Recovery and Rehabilitation in Stroke: Stem Cells.
Stroke 35 (supplement 1): 2691-2694.
 Piccini P, Lindvall O, Bjorklund A et al. (2000) Delayed recovery of movementrelated cortical function in Parkinson’s disease after striatal dopaminergic grafts.
Annals of Neurology 48: 689–695.
 Rossi F & Cattaneo E (2002) Neural stem cell therapy for neurological diseases:
dreams and reality. Nature Reviews in Neuroscience 3: 401-409.
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 improvements?
 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?