Lecture 17 - Stem Cells and Their Use in Therapy Flashcards
Two key properties of stem cells?
- They undergo asymmetric cell division and therefore can self-renew and maintain the stem cell pool.
- They give rise to daughter cells that can differentiate.
Which type of SC has the largest telomeric activity?
Embryonic stem cells - they can survive for longer.
Totipotent?
This occurs briefly in embryogenesis before blastocyst formation. The cells have the ability to develop into an entire organism.
Pluripotent?
Once the blastocyst has formed, the cells of the inner cell mass have the potential to develop into all cell types. They do not form the placenta or supporting tissues and so are unable to develop a new organism entirely on their own.
Blastocyst structure?
- Forms roughly 4-5 days after fertilisation.
- Outer layer of cells = trophectoderm, made of trophoblast cells. These will form the placenta.
- Inside is the inner cell mass and a fluid filled cavity.
How does the teratoma assay determine pluripotency?
A teratoma is a benign cancer. PSCs can differentiate into the 3 germ layers. Inject PSCs into the immunocompromised mouse. If they are truly pluripotent then teratoma growth should show all 3 germ layers.
3 key TFs that control pluripotency of ESCs?
Oct-4, Nanog and Sox2. They activate pluripotent associated pathways and suppress those that promote differentiation.
ESCs have therapeutic potentials = they can be used to replace worn or diseased body parts, for example?
Neurodegenerative diseases, diabetes, corneal defects, cardiovascular disease and musculoskeletal disorders.
Which TFs/GFs are involved in the control of the differentiation of dopamine-producing neurons in the midbrain?
- Nuclear Receptor Related - 1 (Nurr1)
- GFs FGF8 and Sonic hedgehog (Shh).
How have ESCs been used to treat Parkinson’s disease?
- ES cell lines exposed to FGF8 and Shh - showed an increased expression in markers of dopamine-producing neurons.
- Also exposed to TF Nurr1 alongside the GFs. Further up-regulation of marker expression.
- Rat models with induced paralysis were injected with neuronal cells developed from ES cells - showed an improvement in motor function.
Therapeutic cloning vs. Reproductive cloning?
Somatic cell nuclear transfer was the technique used to create Dolly the sheep and is also referred to as reproductive cloning. This involves the fusion of a nucleus from a somatic cell, and an enucleated egg.
Therapeutic cloning is used to generate a blastocyst from which the PSCs of the inner cell mass can be isolated and expanded in vitro.
Give some examples of where ASCs are found.
Bone marrow, colon and skin.
Multipotent?
The SCs can develop into more the one cell type of the tissues they reside. They have a more restricted differentiation potential.
The use of ASCs have fewer therapeutic risks. Why?
No risk of teratome formation as they are not pluripotent. Fewer ethical concerns as embryos are not used for therapeutic purposes.
Examples of ASCs.
- Haematopoietic stem cells.
- Epidermal stem cells.
- Mesenchymal stem cells.
- Neural stem cells.
- Limbal (corneal) stem cells.
