Lecture 9 - Stem Cells & Regeneration Flashcards
What are the two functional characteristics of stem cells?
- Ability to differentiate into different cell types
2. Capacity for self renewal
What is the hierarchy of stem cell potentials?
- Totipotent
- Pluripotent
- Multipotent
- Oligopotent
- Unipotent
What is a ‘committed cell’
It has differentiated and now no longer a stem cell
What is a difference between somatic and stem cells in terms of division
Somatic cell: divides into two identical cells
Stem cells: self-renews, as well as differentiates
At which point in development do we start to see distinct cell types and structures?
Blastocyst stage
Describe the changes that occur to the blastocyst
Inward migration of ICM
Forms primitive streak
Gastrulation; neurulation
Describe how the blastocyst attaches to the wall of the uterus
Trophectaderm merges with the wall
What are the three germ layers, and what is their significance?
• Ectoderm
• Mesoderm
• Endoderm
Each forms different types of organs
Describe the potency of ICM cells
Pluripotent
What are embryonic stem cells?
Pluripotent cells from ICM
What does mesoderm generally go on to form?
- Cardiac muscle
- Skeletal muscle
- Smooth muscle
- Erythrocytes
What does endoderm generally go on to form?
- Alveolar cells
- Thyroid cells
- Pancreatic cells
What does the ectoderm go on to form?
- Skin
* Nervous tissue
What is special about the GIT epithelium?
These stem cells are quite active because the gut epithelium is constantly being sheared off
How are stem cells activated after ischemic injury in the heart?
- Factors released by the ischemic tissue
- Factors act on bone marrow to mobilise cardiac stem cells
- Cardiac stem cells populate the area of injury in an attempt to repopulate area of injury
What are some of the factors given off by ischemic cardiac tissue?
- G-CSF
- SCF
- SDF-1
What are the stem cells for the heart?
Cardiac stem cells
What are the stem cells for the brain?
Neural stem cells
Where are neural stem cells?
Where are cardiac stem cells?
What about GIT stem cells?
Neural: discrete locations in the brain: near lateral ventricles
Cardiac: bone marrow
GIT: crypts
Describe stem cell activation in brain injury
- CNS injury / hypoxia
- Microglial activation
- Astrocyte activation
- Neural stem cell activation
- Migration of NSCs towards injury
What are the major stem cell types?
- Embryonic stem cells
- Embryonic germ cells
- Adult stem cells
- Umbilical cord and placenta stem cells
What are stem cell lines and what are they used for?
- Cells isolated from a blastocyst an maintained as a ‘line’ in the lab
- Can be grown indefinitely
- Used for scientific experiments
What does unipotent mean?
Gives rise to only one specific cell type
What does oligopotent mean?
Give an example
eg. Neural stem cells
Only give rise to 3 cell types
Why are umbilical cord stem cells more useful than adult stem cells?
They are more potent (they are pluripotent)
Embryonic: pluripotent
Adult: multipotent
What is the name of the stem cell microenvironment?
Stem cell niche
Describe stem cell niches
Stem cells exist in a microenvironment with specific factors that are required to maintain the cells
• ECM
• factors
What happens when neural stem cells are removed from their niche?
Stop dividing
The more potent the stem cell, the more …
… plastic the stem cell
Describe adult stem cell plasticity
Endoderm stem cells can give rise to many different cell types; but it is limited to cells that are normally derived from endoderm
What is SCNT?
Somatic cell nuclear transfer
Describe SCNT
Asexual reproduction
- Oocyte with nucleus removed
- Nucleus transplanted into the oocyte
- Electrical stimulus to start dividing
What is SCNT used for?
Cures and therapies for diseases
• through ‘awakening’ capacity for self repair
What are the benefits of SCNT?
• No donor rejection (patient uses their own cells)
Describe how Dolly the lamb was cloned
- Donor oocyte from sheep
- Mammary cell nuclear material transplanted into oocyte from other sheep
- Embryo develops
- Embryo implanted in surrogate mother
- Cloned sheep develops normally
Describe how SCNT could be used to treat Type I Diabetes
- Nucleus from patient cell fused with oocyte
- Blastocyst develops from fused cell
- Embryonic stem cells isolated from inner cell mass
- Pancreatic cells derived from these embryonic stem cells
What are the drawbacks of SCNT?
Well documented cases of individuals developing cancers from the implanted stem cells
What is molecular reprogramming?
What is the basis of this?
Manipulating the potency of a stem cell
• Genetic basis
Describe the induction of pluripotent stem cells
- Somatic cells (eg. fibroblasts) treated with 4 transcription factors
• c-myc etc. - iPS
What are iPS?
Induced pluripotent stem cells
Describe stress stimulus triggered acquisition of pluripotency
Somatic cells treated with three stressors:
• bacterial toxin
• exposure to low pH
• physical stretching of membrane
Compare iPS and stress stimulus triggered stem cells
The new system is much more efficient at producing stem cells
Describe tissue engineering
- Heart taken out of animal and kept alive with nutrient etc.
- De-cellularise (only ECM left)
- Infuse cardiac stem cell into de-cellularised heart
- Production of functional heart
Describe tissue engineering in humans
Only one instance:
• Replacement of oesophagus
• Considerable success
What is the connection between stem cells and malignant cells
• deregulation of stem cell microenvironment
What are CSCs?
Cancer stem cells
What happens in cancer treatments that don’t target CSCs?
The tumous cells die, but the tumour grows back, because the CSC is still present
What happens in cancer treatment that targets CSCs?
Much better effect, because the cancer loses the ability to regenerate
Describe these features of adult stem cells:
• location
• potency
• presence
Location: near or in the tissue
Potency: can form functional cells within their tissue type, but not others
Presence: only in tissues that experience regular turnover; presence decreases with age
Describe the features of umbilical / placental stem cells
- isolated just after birth
- more potency than adult stem cells, but not as potent as embryonic SCs
- current area of research
- can be banked for future use
What are the sources of adult stem cells?
- Bone marrow
- Cardiac muscle
- Neural cells
What is the ethical question that surrounds stem cell therapeutics?
Whether to use adult or embryonic stem cells
What are the cons of ES?
(embryonic stem cells)
• Non-self
• Ethical issues
What are the pros of SCNT?
Self
What are the cons of SCNT?
- Inefficient process
* Oocytes are hard to come by
What are the cons of iPS?
• Inefficient & labour intensive
What are the cons of adult stem cells?
- Grow poorly
- Accessibility
- Can not give rise to very many cell types
