Adult Stem Cells Flashcards
Define adult stem cells.
Cells that can self-renew and have the ability to differentiate, generating cells with different functions.
Define multipotent, pluripotent and totipotent stem cells.
- Multipotent - can differentiate into multiple cell types within a lineage
- Pluripotent - can differentiate into all cell types in the adult
- Totipotent - can differentiate into all cell types of all embryonic and adult lineages
What is a cell lineage?
- All cells are derived from 3 layers of embryo -ectoderm, mesoderm, endoderm
- Each of these layers is a cell lineage
What is the intermediate step between a multipotent stem cell and a differentiated cell?
Progenitor cell
Explain the difference between symmetric and asymmetric cell division.
- Symmetric - produces 2 daughter cells of the same stem cell lineage
- Asymmetric - produces 1 stem cell and 1 progenitor cell
What does the cell microenvironment - or niche - determine about stem cells?
Microenvironment determines whether a SC remains quiescent, proliferates or differentiates
Why is the extracellular matrix and important component of the cell microenvironment?
- Scaffolding maintains 3D architecture of tissue
- Critical regulator of stem cell function
- Can determine cell fate via mechanical features - e.g. brain “stiffness” induces neuron formation
- Reservoir for growth factors via heparin sulfate proteoglycan binding
What are telomeres and what happens to them when cells divide? How does this relate to telomerase and adult stem cells?
- Telomeres are repetitive sequences on the tip of chromosomes
- Telomeres shorten gradually over repeated cell divisions
- Telomerase replenishes telomeres and prevents cell senescence - division halts
- Most adult stem cells have low or absent telomerase activity
- In tissues that need to replenish cells constantly, there is still some telomerase activity
Explain the advantages and disadvantages of using adult stem cells in therapy.
Advantages:
- Fewer ethical problems than embryonic SC
- Lower risk than embryonic SC
- Autologous transplantation
Disadvantages:
- Lower differentiation capacity
- Heterogeneous population
- Difficult to obtain in sufficient numbers
Explain what mesenchymal stem cells are.
- MSCs must be purified from the bone marrow stromal population based on plastic adherence under standard culture conditions
- MSCs must be positive for CD105, CD90, and CD73, express low levels of MHC-I, and be negative for MHC-II, CD11b, CD14, CD34, CD45, and CD31
- MSCs must at least differentiate in vitro into osteocytes, chondrocytes, and adipocytes
Explain the therapeutic potential of mesenchymal stem cells.
- Homing capacity - tendency to find and integrate into damaged tissue sites
- Good differentiation potential
- Production of trophic factors - protect other stem cells
- Secrete immunomodulatory molecules that prevent inflammation
What is limbal stem cell therapy used for?
- Corneal renewal and repair are mediated by stem cells of the limbus, the narrow zone between the cornea and the bulbar conjunctiva
- Used for patients with burn-related limbal stem cell deficiency
- Autologous limbal stem cells (3000) obtained and cultured on fibrin before transplantation
What is cell transdifferentiation?
- Adult cells differentiate into other cell types either directly or indirectly
- Direct - e.g. osteoblast > adipocyte
- Indirect - e.g. osteoblast > mesenchymal stem cell > adipocyte
How has transdifferentiation therapy been used?
- Overexpression of Pax4 genes in pancreatic alpha cells restores functional beta cells and reverses diabetes in animals that have been chemically depleted of beta cells
- Progenitor cells differentiate into alpha cells
- Alpha cells differentiate into beta cells
Outline the different models of cancer stem cells.
- Hierarchical model - limited number of CSCs within tumour - implies that tumour growth can be halted by destroying CSCs
- Stochastic model - every cell in a tumour has the capacity to become a CSC
- Cellular plasticity model - combination of other two - there is a specific subset of tumour-initiating cells, but differentiated cells can enter this pool if they undergo mutations in stem-like genes
