(PM3A) Stem Cells in Health & Disease Flashcards
What is a stem cell?
Cells
Self-renew – can generate new cells
Differentiate into all cells of a particular lineage/ tissue
What are ESCs?
Embryonic stem cells
What is a fertilised egg called?
Zygote
What is a blastocyst?
Contains inner cell mass
Where is the inner cell mass found?
Blastocyst
What is the ICM?
Inner cell mass
Where are embryonic stem cells derived from?
Inner cell mass
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
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
What are neural stem cells?
Stem cells which give rise to cells of the nervous sytem
Multipotent - tissue-specific (adult)
What are hematopoietic stem cells?
Stem cells which give rise to cells of the nervous system
Multipotent - tissue-specific (adult)
What is cellular differentiation?
Cell goes from less specialised to a more specialised state
How can the differentiation of stem cells be driven in vitro?
(1) Developmental approach
(2) Empirical approach
What is an empirical approach, with regard to differentiation of stem cells in vitro?
Factors/ conditions that drive cells to differentiate to particular lineages
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
What are progenitor cells?
Early descendants of stem cells
What is the intermediary molecule between B cells, T cells, NK cells, and dendritic cells from hematopoietic cells?
Lymphoid progenitor
What is the intermediary molecule between erythrocytes and platelets from hematopoetic cells?
Myeloid progenitor
Describe the potency of embryonic stem cells.
Pluripotent
What types of cell can be generated from pluripotent stem cells?
Any type of cell
Brain, liver, heart, blood etc
Name some sources of adult-derived (tissue-specific) stem cells.
Bone marrow
(1) Hematopoietic stem cells
(2) Mesanchymal stem cells
What do hematopoietic stem cells differentiate to?
Blood cells
What do mesenchymal stem cells differentiate to?
(1) Osteoblasts - bone
(2) Myocytes - muscle
(3) Adipocytes - fat
(4) Chondrocytes - cartilage
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
