Download Neurowiki Group: Stem Cell Therapies in Neuroscience Members

Neurowiki Group: Stem Cell Therapies in Neuroscience
Members: Riasat Ahmed, Michael Jungmin Son, Janice Siu Yan Hui, Romeo Alex Penheiro, Sara Shu Fen
Chung, Salwa Hasan
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 bonemarrow 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 selfrepair. 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.
1. Multiple Sclerosis (MS) (Riasat Ahmed)
a. Drawbacks in current therapy
b. Transplanting Mesenchymal Stem Cells
- How is it delivered? Intravenous delivery
- Promotion of myelin repair and reduction of glial scar formation
- Effectiveness of treatment and trials
2. Alzheimer’s Disease (AD) (Michael Jungmin Son)
2.1 neural stem cell (NSC)
a) effect of neurosphere on mouse model of nucleus basalis of Meynert (NBM) lesion
b) cognition improvement via brain-derived neurotrophic factor (BDNF)
2.2 basal forebrain grafts of fibroblasts
a) nerve growth factor (NGF) gene therapy
2.3 cholinergic neurons
a) transplantation of fetal cholinergic neurons
3. Huntington’s Disease (HD) (Janice Siu Yan Hui)
a. Neural stem cells repaired the function of damaged GABAergic neurons
b. Animal models of HD and further research with stem cells on HD
4. Parkinson’s Disease (PD) (Romeo Alex Penheiro)
a. Use of different types of stem cells for the therapy of PD
b. GABAergic cell transplantation into the dopaminergic neurons in striatum
c. Evidence from animal models showing improved behavioral symptoms of PD
d. Current progress of clinical trials for the disease
5. Stroke (Sara Shu Fen Chung)
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
6. Spinal cord injury (Salwa)
a. Various stem cell therapies attempted for spinal cord injury
b. Neural stem cell therapy acting through secondary mechanisms
c. Mesenchymal stem cells providing long term effects in SCI
d. Importance of remyelination of neural stem cells
Words: 508
[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.
Reference:
1) Martinez-Cerdeno, V. et al. Embryonic MGE Precursor Cells Grafted into Adult Rat Striatum
Integrate and Ameliorate Motor Symptoms in 6-OHDA-Lesioned Rats. Cell Stem Cell (2010)
6(3):238-250
2) Lin Y. C., Ko T. L., Shih Y. S., Lin A. M., Fu T. W., Hsiao H. S., Hsu J. C., Fu Y. S. Human
Umbilical Mesenchymal Stem Cells Promote Recovery After Ischemic Stroke. Stroke. (2011)
42: 2035-2053
Regenerative medicine in neuroscience
Hey everyone,
We were thinking about having neuroregenerative medicine and the use of Stem cells to treat
certain diseases. After some preliminary research some diseases are listed below. Please pick
one topic of interest from the list below. We also need one person (or may be small groups to
take the Introduction and Conclusion)
Also, please do more research on the topic you would like to go with! If none of the topics are to
your interest then please find a topic relating to stem cells and neurodegenerative disease and
work on that. Don’t forget to write it down here, so we know what you’re working on. Also, if you
have any critical suggestions please don’t hesitate to point out.
hey guys, just a thought: would stroke/tumours/spinal cord injury classify as neuro‘degenerative’ diseases?
Introduction
Regenerative medicine is the process of creating living, g functional tissues to repair or replace
tissue or organ function lost due to age, disease, damage, or congenital defects.
- Regenerative medicine, NIH fact sheet (http://report.nih.gov/NIHfactsheets/Pdfs/Reg
enerativeMedicine%28NIBIB%29.pdf)
What are stem cells and why use them for nerve regeneration?
- Stem cells are not terminally differentiated and can be made to differentiate (under the right
conditions) … they can be pluripotent (that is, give rise to all cell types of the body) or
multipotent (give rise to specific tissue types)
- They have the capacity for self-renewal (divide without limit)
How to get stem cells?
Adult and embryonic stem cells (including induced pluripotent stem cells)
http://biomed.brown.edu/Courses/BI108/BI108_2001_Groups/Nerve_Regeneration/
- Embryonic stem cells are obtained from the inner cell mass of a blastocyst
- Pluripotent
- Adult stem cells are obtained from specific mature body tissues, umbilical cord, placenta, bone
marrow, etc.
- Generally multipotent but can also be induced pluripotent stem cells
Main (Choose 1)
Parkinson’s disease - Romeo
http://www.ncbi.nlm.nih.gov/pubmed/21651331
Spinal cord injury - Salwa
http://www.ncbi.nlm.nih.gov.myaccess.library.utoronto.ca/pubmed/22271661
Alzheimer’s disease - Mike
http://www.ncbi.nlm.nih.gov/pubmed/21495961
Stroke - Sara
http://www.ncbi.nlm.nih.gov/pubmed/21757669
Multiple sclerosis - Riasat
http://www.ncbi.nlm.nih.gov/pubmed/21683930
Cancer - Janice
http://www.ncbi.nlm.nih.gov/pubmed/21549324
Conclusion:
Potential uses of stem cells
Cost and benefits
Ethics and barriers to clinical trials
Challenges with regenerative medicine:
• Protocols for mice – not always same for humans
• Increasing scale
• Use of good manufacturing practices, avoidance of bacterial or mammalian cell contaminants
• Better methods to vascularize engineered organs needed
• Protocols to grow cells in 3D on suitable scaffolds needed
• Better biomaterials (incorporating nanotechnology)
• For preclinical studies need several animal models
• Therapy must be a better option than current therapies
Challenges with use of stem cells: Cancer
• Less differentiated cells have a greater tendency to become cancerous (including teratomas)
• If viruses used to alter cell fate could integrate into endogenous tumour suppressor gene or
oncogene
• With allogeneic cells still have to immunosuppress
• iPS cells develop mutations (base changes, copy number variations, difference in
chromosome #) and epigenetic changes