Lecture 9 - Stem Cells & Regeneration Flashcards by Eleanor Nicklason

What are the two functional characteristics of stem cells?

Ability to differentiate into different cell types

2. Capacity for self renewal

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What is the hierarchy of stem cell potentials?

Totipotent
Pluripotent
Multipotent
Oligopotent
Unipotent

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What is a ‘committed cell’

It has differentiated and now no longer a stem cell

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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

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At which point in development do we start to see distinct cell types and structures?

Blastocyst stage

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Describe the changes that occur to the blastocyst

Inward migration of ICM
Forms primitive streak
Gastrulation; neurulation

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Describe how the blastocyst attaches to the wall of the uterus

Trophectaderm merges with the wall

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What are the three germ layers, and what is their significance?

• Ectoderm
• Mesoderm
• Endoderm
Each forms different types of organs

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Describe the potency of ICM cells

Pluripotent

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What are embryonic stem cells?

Pluripotent cells from ICM

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What does mesoderm generally go on to form?

Cardiac muscle
Skeletal muscle
Smooth muscle
Erythrocytes

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What does endoderm generally go on to form?

Alveolar cells
Thyroid cells
Pancreatic cells

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What does the ectoderm go on to form?

Skin

* Nervous tissue

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What is special about the GIT epithelium?

These stem cells are quite active because the gut epithelium is constantly being sheared off

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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

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What are some of the factors given off by ischemic cardiac tissue?

G-CSF
SCF
SDF-1

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What are the stem cells for the heart?

Cardiac stem cells

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What are the stem cells for the brain?

Neural stem cells

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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

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Describe stem cell activation in brain injury

CNS injury / hypoxia
Microglial activation
Astrocyte activation
Neural stem cell activation
Migration of NSCs towards injury

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What are the major stem cell types?

Embryonic stem cells
Embryonic germ cells
Adult stem cells
Umbilical cord and placenta stem cells

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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

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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 1. Oocyte with nucleus removed 2. Nucleus transplanted into the oocyte 3. 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

1. Donor oocyte from sheep 2. Mammary cell nuclear material transplanted into oocyte from other sheep 3. Embryo develops 4. Embryo implanted in surrogate mother 5. Cloned sheep develops normally

Describe how SCNT could be used to treat Type I Diabetes

1. Nucleus from patient cell fused with oocyte 2. Blastocyst develops from fused cell 3. Embryonic stem cells isolated from inner cell mass 4. 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

1. Somatic cells (eg. fibroblasts) treated with 4 transcription factors • c-myc etc. 2. 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

1. Heart taken out of animal and kept alive with nutrient etc. 2. De-cellularise (only ECM left) 3. Infuse cardiac stem cell into de-cellularised heart 4. 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