EXAM 2 - Session 19: Stem Cells - Tissue Maintenance and Repair

Question 1

Describe how stem cells are used as therapy method for Parkinson’s disease.

Answer 1

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

Question 2

Explain the negative drug side-effect of patient stem cells.

Answer 2

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

Question 3

Explain the positive drug targeting of stem cells.

Answer 3

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

Question 4

Describe the functional abilities of stem cells?

Answer 4

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)

Question 5

Explain how stem cell progenies are categorized.

Answer 5

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

Question 6

Define unipotent.

Answer 6

Produces:
* daughter cell 1 - 1 cell type specialization (ex. replicating adult skin cells)
* daughter cell 2 - stem cell

Question 7

Define multipotent.

Answer 7

Produces:
* daughter cell 1 - can producemany specializations of cells
* daughter cell 2 - stem cell

Question 8

Define pluripotent.

Answer 8

Produces:
* daughter cell 1 - embryonic cell: can produce cells of any tissue or body layer
* daughter cell 2 - stem cell

Question 9

Define totipotent.

Answer 9

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

Question 10

What are the three sources of stem cells?

Answer 10

• 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)

Question 11

Describe embryonic stem cells derived from inner cell mass (ICM).

Answer 11

• 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)

Question 12

Describe how pluripotent ICM-derived ES cells were used in a mouse model system to treat diabetes.

Answer 12

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

Question 13

Describe somatic stem cells in the adult.

Answer 13

Somatic stem cells in specialized, self-renewing tissue
* varying degrees of potency characteristic of tissue
* unipotent - epidermis, gut lining
* multipotent - bone marrow

Question 14

Describe hemotopoietic stem cells in the adult.

Answer 14

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

Question 15

Explain the small intestine epithelium example of self-renewal from very low potency intestinal stem cells (ISC)

Answer 15

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

Question 16

Define villus.

Answer 16

The tip of the intestinal villi.

Question 17

Define crypt.

Answer 17

The base of the villus

Question 18

Define TA cell compartment.

Answer 18

Transit amplifying cell compartment
* progeny of stem cells
* TA can only replicate 2-3 times

Question 19

Define enterocytes and goblet cells.

Answer 19

Come from TA cells and make up the surface of the villus

Question 20

Explain APC: adenomatous polyposis coli. What is it? What does it do?

Answer 20

• 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

Question 21

Define adenoma.

Answer 21

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

Question 22

Explain induced pluripotent stem (iPS) cells.

Answer 22

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

Question 23

Name the 4 genes that are typically expressed in ES cells and are inserted into the adult genome through iPS cells.

Answer 23

OCT4, c-MYC, SOX2, KLF4

Question 24

How are stem cells used in basic research and drug discovery/testing?

Answer 24

• wound repair
• caspase activity in apoptosis
• use specialized cell types for petri dish testing for cell-type depedent toxicity/efficacy of new drugs

Question 25

How are stem cells used in cell based therapies?

Answer 25

• 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…