(PM3A) Stem Cells in Health & Disease Flashcards by David Vincent-Waterson

What is a stem cell?

Cells

Self-renew – can generate new cells

Differentiate into all cells of a particular lineage/ tissue

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What are ESCs?

Embryonic stem cells

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What is a fertilised egg called?

Zygote

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What is a blastocyst?

Contains inner cell mass

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Where is the inner cell mass found?

Blastocyst

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What is the ICM?

Inner cell mass

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Where are embryonic stem cells derived from?

Inner cell mass

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What are the 3 germ layers?

(1) Ectoderm - outer part, e.g. nervous system
(2) Mesoderm - middle part, e.g. musculoskeletal system
(3) Endoderm - inner part, e.g. respiratory/ digestive systems

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How is the potency of stem cells classified?

(1) Totipotent – give rise to any cell type
(2) Pluripotent – any cell of the body
(3) Multipotent – any cell of specific lineage/ tissue

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What are neural stem cells?

Stem cells which give rise to cells of the nervous sytem

Multipotent - tissue-specific (adult)

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What are hematopoietic stem cells?

Stem cells which give rise to cells of the nervous system

Multipotent - tissue-specific (adult)

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What is cellular differentiation?

Cell goes from less specialised to a more specialised state

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How can the differentiation of stem cells be driven in vitro?

(1) Developmental approach

(2) Empirical approach

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What is an empirical approach, with regard to differentiation of stem cells in vitro?

Factors/ conditions that drive cells to differentiate to particular lineages

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What is a developmental approach, with regard to differentiation of stem cells in vitro?

Knowledge that cells respond to extracellular cues/ cell-cell contact

Understanding of cell fates

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What are progenitor cells?

Early descendants of stem cells

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What is the intermediary molecule between B cells, T cells, NK cells, and dendritic cells from hematopoietic cells?

Lymphoid progenitor

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What is the intermediary molecule between erythrocytes and platelets from hematopoetic cells?

Myeloid progenitor

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Describe the potency of embryonic stem cells.

Pluripotent

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What types of cell can be generated from pluripotent stem cells?

Any type of cell

Brain, liver, heart, blood etc

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Name some sources of adult-derived (tissue-specific) stem cells.

Bone marrow

(1) Hematopoietic stem cells
(2) Mesanchymal stem cells

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What do hematopoietic stem cells differentiate to?

Blood cells

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What do mesenchymal stem cells differentiate to?

(1) Osteoblasts - bone
(2) Myocytes - muscle
(3) Adipocytes - fat
(4) Chondrocytes - cartilage

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What are NSCs?

Neural stem cells

What can neural stem cells differentiate to?

(1) Neurons (2) Oligodendrocytes (3) Astrocytes

What is somatic cell nuclear transfer?

First method shown to reprogram adult cell to pluripotency

How can we generate patient-specific stem cells?

Somatic cell nuclear transfer (SCNT) (1) Transfer of nucleus from somatic cell to enucleated egg (2) Generates a developing embryo via blastocysts

How are embryonic stem cells generated via somatic cell nuclear transfer different from those generated in vitro?

Genetic code comes from donor somatic cell Resulting cells have DNA from somatic cell (patient/ disease-specific)

What are some of the ethical objections to the generation and use of embryonic stem cells?

(1) Usually derived from unused IVF embryos | (2) Destruction of viable embryo

What are some technical limitations of embryonic stem cell use?

Cannot be made from individual patient

Do ALL embryonic stem cells have ethical | complications?

Yes

What types of pluripotent stem cells are there?

(1) Embryonic stem cells (2) Somatic cell nuclear transfer (3) Induced pluripotent stem cells (hiPSCs in humans)

What is the benefit of induced pluripotent stem cells (iPSCs)?

No need to generate an embryo

What are induced pluripotent stem cells?

Reprogrammed somatic cells directly into a stem cell Using 4 transcription (Yamanaka) factors

What are the four transcription factors used in induced pluripotent stem cells?

(1) Oct3/4 (2) c-Myc (3) Klf4 (4) Sox2

Which cell was first used for induced pluripotent stem cells (iPSCs)?

Mouse fibroblasts

What are some benefits of iPSCs compared to embryonic stem cells (ESCs)?

(1) ESCs limited in availability (2) ESCs limited in versatility (3) Fewer ethical issues with iPSCs (4) iPSCs give rise to possibility of personalised medicine (5) Can be generated from any individual (6) Carry genetics of individual gotten from (7) Can use iPSCs to develop models of disease for regenerative medicine

Which types of generated stem cells have risks of tumorigenicity?

Both ESCs and iPSCs (1) Embryonic stem cells (2) Induced pluripotent stem cells

Where can multipotent stem cells be sourced?

(1) Pluripotent stem cells | (2) Adult stem cells in the body, e.g. bone marrow

How can multipotent (adult) stem cells be used in developmental biology and basic research?

(1) Understanding disease + drug discovery | (2) Cell-based therapy

How can stem cells be used in regenerative medicine?

(1) Bone marrow transplantation, HSCs (hematapoietic) (2) Crohn's disease (3) Blindness (4) Deafness (5) Baldness (6) Missing teeth (7) Spinal chord injury

What stem cells are being used in clinical trials?

(1) Hematopoietic stem cells – immunoablation for multiple sclerosis (2) iPSCs – age-related macular degeneration (AMD), Parkinson's, etc (3) Embryonic stem cells – pancreatic beta cells for T1DM, ischaemia heart disease, macular degeneration (4) Mesanchymal stem cells – for secretions of factors + immune modulation properties (5) Neural stem cells – spinal chord injury, also for secretion of factors

How can disease-specific/ patient-specific stem cells be generated?

From iPSCs Induced pluripotent stem cells

What types of stem cells are very difficult to acquire?

Neuron stem cells (NSCs) From CNS

What is a benefit of developing a disease-specific tissue compared to healthy tissue using human iPSCs?

Can identify differences between healthy + disease cells Produce a phenotypic model Can distinguish phenotypic differences Identify events in disease progression Test drugs for toxicity/ efficacy Discovery of new drug targets

Which disease mutations may cause Alzheimer's disease?

(1) PSEN1 (2) PSEN2 (3) APP

How can neural stem cells be generated?

From hiPSCs Differentiated into different types of neurons/ astrocytes/ oligodendrocytes

What are microglia?

Key cell of the brain Immune system of the brain Different lineage from neurons/ oligodendrocytes/ astrocytes

How can be microglia be generated?

Derived from non-neural lineage hiPSCs

What is Alzheimer's disease?

Neurodegenerative disorder Can be familial/ sporadic

What are some hallmarks of Alzheimer's disease?

(1) Extracellular plaques of amyloid beta (Aß) | (2) Intracellular tangles of hyperphosphorylated Tau

What is the amyloid hypothesis?

Accumulation of amyloid beta (Aß) peptide aggregates

What is a potential benefit of hiPSCs in Alzheimer's disease?

(1) Human models of Alzheimer's in vitro | (2) Able to explore differences between familial + sporadic Alzheimer's disease

What is an isogenic control?

In modelling A tissue with a disease which has had the mutation corrected

What is fAD?

Familial Alzheimer's disease

What is sAD?

Sporadic Alzheimer's disease

What percentage of all Alzheimer's disease cases does fAD account for?

~5%

What percentage of all Alzheimer's disease cases does sAD account for?

~95%

What is a zygote?

Fertilised egg cell