EXAM 2 - Session 19: Stem Cells - Tissue Maintenance and Repair Flashcards
Describe how stem cells are used as therapy method for Parkinson’s disease.
Donor-derived stem cells are transplanted into a Parkinson’s patient
* goal: the stem cells will mature into cells that will help slow the progession of the disease
Explain the negative drug side-effect of patient stem cells.
Example: Dexamethasone - synthetic analogue of cortisol (anti-inflammatory)
* induces specialization adult blood somatic stem cells to mature progeny cells (non-replicating)
* stem cells are pushed to post-mitotic compartment
Explain the positive drug targeting of stem cells.
Example: PGE2 stimulates adult blood somatic stem cell replication
* PGE2 - prostaglandin type E2: bioactive lipid
* collects donor cells and increases replication with PGE2 in lab before transplant into patient
* originally found with zebra fish screening
Describe the functional abilities of stem cells?
Renew (self-replicate) an indefinite number of times
* typically have high telomerase levels
Replenishment/repair of tissue
* 1 daughter cell stays a stem cell with high replication ability (maintains stem cell population)
* 1 daughter cell matures into specialized cells typical for that tissue (limited # of cell division ability)
Explain how stem cell progenies are categorized.
Range of progeny reflects potency of stem cell.
(potency - the varying ability of stem cells to differentiate into specialized cell types)
* unipotent, multipotent, pluripotent, totipotent
Define unipotent.
Produces:
* daughter cell 1 - 1 cell type specialization (ex. replicating adult skin cells)
* daughter cell 2 - stem cell
Define multipotent.
Produces:
* daughter cell 1 - can producemany specializations of cells
* daughter cell 2 - stem cell
Define pluripotent.
Produces:
* daughter cell 1 - embryonic cell: can produce cells of any tissue or body layer
* daughter cell 2 - stem cell
Define totipotent.
Produces:
* daughter cell 1 - generates all cells and tissue types of an embryo (most diverse range of daughter cell development
* daughter cell 2 - stem cell
What are the three sources of stem cells?
- ESC - embryonic stem cells (from ICM)
- post-natal or adult “somatic” stem cells (for tissue replenishment) - found in regenerating tissues
- induced pluripotent stem cells (iPSCs)
Describe embryonic stem cells derived from inner cell mass (ICM).
- totipotent: fertilized egg forms 2 cell embryo –> replicates into multiple cells
- pluripotent: solid ball of embryonic cells lose potency and hollow out
- ICM cells generate all the body tissues of the developing embryo
- pluripotent cells generate the endoderm, mesoderm, ectoderm, and ES cells (pluripotent)
Describe how pluripotent ICM-derived ES cells were used in a mouse model system to treat diabetes.
Mouse ES cells were differentiated into insulin-secreting clusters that acted very similar to pancreatic islets
* in the petri dish, clusters of ES cells responded to glucose by secretin insulin
* insulin-secreting clusters were implanted in mouse diabetes model and challenged with glucose
* result: insulin production partially reversed diabetes
Describe somatic stem cells in the adult.
Somatic stem cells in specialized, self-renewing tissue
* varying degrees of potency characteristic of tissue
* unipotent - epidermis, gut lining
* multipotent - bone marrow
Describe hemotopoietic stem cells in the adult.
Multi-potent cell renewal
* progressive stages have decreased replication ability
* once committed down a line, there is no side-to-side changing
* CLP/CMP –> committed progenitors –> mature cells
Explain the small intestine epithelium example of self-renewal from very low potency intestinal stem cells (ISC)
ISC have lifetime renewal capacity
* ISC divide to produce 1 ISC and 1 transient amplifying TA cell (aka limited replication cell)
* TA cells go through limited cell cycles
* their progeny differentiate into globet cells and enterocytes
Define villus.
The tip of the intestinal villi.
Define crypt.
The base of the villus
Define TA cell compartment.
Transit amplifying cell compartment
* progeny of stem cells
* TA can only replicate 2-3 times
Define enterocytes and goblet cells.
Come from TA cells and make up the surface of the villus
Explain APC: adenomatous polyposis coli. What is it? What does it do?
- tumor supressor gene
- mutations in most colon cancers and some other cancers (like liver) –> because “break” doesn’t work and replication is unregulated
- acts as a break or limitation on the cell cycle –> regulates cell replication
Define adenoma.
A mass of over-proliferating epithelial cells
* a tumor that is not cancerous
* caused from the lack of APC –> TA cell replication is not regulated
* TA cells don’t have a limited number of replication cycles anymore –> accumulation in the TA compartment
Explain induced pluripotent stem (iPS) cells.
Adult cells are genetically reprogrammed to an ESC-like, pluripotent state.
* iPS cells are injected into early embryo and contribute to ALL types of embryonic tissues (like ES cells)
* 4 different genes that are typically expressed in ES cells are inserted into adult cell genome using viruses
* result: loss of adult cell-specific function and gain of ES-like pluripotency
Name the 4 genes that are typically expressed in ES cells and are inserted into the adult genome through iPS cells.
OCT4, c-MYC, SOX2, KLF4
How are stem cells used in basic research and drug discovery/testing?
- wound repair
- caspase activity in apoptosis
- use specialized cell types for petri dish testing for cell-type depedent toxicity/efficacy of new drugs
How are stem cells used in cell based therapies?
- cause maturation of stem cells in petri dish to specific cell types and transplant back into patient for regeneratice/replacement therapy
- parkinson’s, alzheimer’s, spinal cord injury, stroke, severe burns, diabetes, oesteoarthritis, etc…
