Introduction to stem cells (CURRENTLY DECK FROM NEUROLOGY MINOR) Flashcards
What are the three most important properties of stem cells?
A stem cell is able to:
- divide
- self-renewal
- differentiate
Explain the meaning of a stam cell that is termed as:
- Totipotent
- Pluripotent
- Multipotent
- Totipotent → stem cell can differentiate in any cell type
- Pluripotent → stem cell can differentiate into any cell types that belongs to one of the three germ layers
- Multipotent → stem cell can only differentiate in the cell types that are present in specific issue
What sources are there for stem cells (i.e. how/where can we get stem cells for e.g. research)?
- Embryonic stem cells are pluripotent (we can isolate and use them)
- Embryonic germ cells
- Tissue stem cell
- Nuclear reprogramming of somatic cells into embryonic stem cell (ESC)-like cells.
How are induced pluripotent stem cells (iPSCs) generated?
Somatic cells, like fibroblasts can be converted into iPSCs with the use of Yamanaka factors. By introducing 4 Yamanaka factors with the help of retroviruses, specialized cells can be reprogrammed into EPSCs.
What are Yamanaka factors, also name examples?
Factors/genes that are expressed or have an important role in ES cells. 24 candidate genes have been identified; Oct3/4, Sox2, KIf4 and c-Myc are examples of these Yamanaka factors.
Name examples of iPSC technology
- Disease modeling
- Drug development
- Cell replacement therapy
- Postmortem means that you are only able to study the end-stage of the disease.
- The use of animal models means that the lab mice typically have one genetic background and that there are differences in species.
How can iPSCs be used in in vitro disease modeling?
Skin cells from a control and a patient are taken and induced as pluripotent stem cells. These cells can then be differentiated in certain cell types that are important for disease modeling. You can then use these differentiated cells to e.g. compare the control with the differentiated cells from the patient by e.g. DNA-microarray analysis.
What kind of information does iPSC technology gives us?
- Background of human cells and genetics
- More information about the different developmental stages
- Specific cell types
- Cellular mechanisms / pathways
What is a disadvantage of using iPSC-derived neurons from AD patients?
Not all patient iPSC-derived cells respond the same
So what do patient-specific iPSCs provide (like what is discussed in AD patients)?
- You can monitor/research disease pathogenesis, irrespective of the disease being in a familial or sporadic form.
- It is possible to evaluate the drug and patients classification of AD.
What is a major advantage of cell replacement therapy (personalized medicine)?
Transplantation of patient-own stem cell derivatives avoids ethical issues and rejection after transplantation.
Name one general challenge of iPSC technology and what is needed to overcome this challenge.
Generation of specific cell types → purity (mixed cultures), functionality (immature cells), characterization (lack of lineage/cell-specific markers).
It is thus needed to improve differentiation protocols.
Name another general challenge of iPSC technology and what is needed to overcome this challenge.
Variability → there’s variability between experiments (variety in maturation stages or replicates) and variability within patient population (phenotype). So cellular reprogramming and differentiation protocols need to be standardized and patients need to be selected based on genetic background.
What is a challenge of iPSC technology in modelling neurodegenerative disorders?
Age:
- Old cells reprogram less well.
- It takes years to develop a phenotype from an immature cell to an aged neuron. It is a long protocol, which also means that it’s vulnerable for variability.
- Besides that, iPSC reprogramming erases epigenetic memory.
