Chapter 5- Stem Cell properties

What is the source of all mature cells in the body?

Stem cells are the source of all mature cells in the body.

Which tissues have stem cells?

The more proliferating tissues all have proficient stem cell systems. Same is true of organs with lower turnover times such as liver, brain pancreas etc, just in a lower concentration.

What are the most common sites for isolation of stem cells?

The most common sites for isolation of stem cells are:
The bone marrow which have hematopoietic and mesenchymal cells
Adipose which have the mesenchymal cell
and cord blood which have unrestricted somatic stem cell.

What are stem cells?

Stem cells are cells that can (1) self-renew (i.e. make identical copies of themselves) and (2) have the ability to differentiate (i.e. form other cell types of the body).

The kinds of progeny a cell can produce determine how it is named. What are the 5 kinds of progeny can a stem cell produce?

Unipotent
Oligopotent
Multipotent
Pluripotent
Totipotent

What does it mean by unipotent Stem cells?

Unipotent stem cells means that they can produce only one cell type

What does it mean by oligopotent stem cells?

Oligopotent stem cells means that they can produce two or more cell types like neural stem cells.

What does it mean by Multipotent stem cells?

Multipotent stem cells means that they have the ability to form multiple cell types (MSCs)

What does it mean by Pluripotent stem cells?

Pluripotent stem cells means that tehy are able to form all three germ layers

What does it mean by Totipotent stem cells?

Totipotent stem cells means that they can produce an entire organism like fertilized oocyte

General division of stem cells. Stem cells can be divided into embryonic and adult/somatic stem cells. Explain each term.

Embryonic are responsible for embryonic and fetal development.
Adult are responsible for growth, tissue maintenance, and regeneration of diseased/damaged tissue.

What fraction of adult tissues are stem cells?

By a large margin, most cells in adult tissues are mature, differentiated cells.

In adipose, the concentration is similar to the bone marrow (1 in 100,000), but access to the tissue is considerably

easier.

What is the difference between adult stem cells and embryonic stem cells?

Adult stem cells are tissue specific cells. For example, the Bone marrow contains hematopoietic and mesenchymal stem cells which can differentiate into blood and connective tissue lineages.
Embryonic stem cells are derived from early embryo prior to commi

What is stem cell plasticity?

Stem cells plasticity is when a stem cell is able to differentiate along different lineages when placed in an appropriate environment. For many years it was thought once a stem cell committed to a tissue it became restricted to that lineage.

How does plasticity due?

Plasticity may be due to non-homogeneous cell populations. Another explanation is potential cellular fusion i.e cells adopting phenotype of surrounding cells.

What is True plasticity?

True Plasticity results in differentiation outside of the stem cells own tissue. Therefore hybrid, heterogeneous, are not generator of true plasticity.

Is Differentiation one-way street?

No, Differentiation is not necessarily a one-way street. There can be Dedifferentiation, redifferentiation, and transdifferentiation.

Example of dedifferentiation.

Some differentiated cells can dedifferentiate into a less mature phenotype. For example, Chondrocytes will lose phenotype when removed from their preferred environment but will redifferentiate into chondrocytes given appropriate cues.

Example of transdifferentiation.

Transdifferentiation is a switch of a differentiated cell into another differentiated cell.
Does not necessarily involve dedifferentiation and redifferentiation.
Caused by a sudden shift of gene expression
Can be induced in vitro by modifying gene express

Example of redifferentiation.

Chondrocytes will lose phenotype when removed from their preferred environment but will redifferentiate into chondrocytes given appropriate cues.

Transdifferentiation is a switch of a differentiated cell into another differentiated cell and does not necessarily involve dedifferentiation and redifferentiation. what causes it?

it is caused by a sudden shift of gene expression. It can be induced in vitro by modifying gene expression (pancreatic cells to hepatocytes) but its occurrence in vivo is debated.

Do stem cells really self-renew?

Yes. During a stem cell division one or both of the daughter cells can maintain the stem cell phenotype. Stem cells can divide symmetrically or asymmetrically.

During a stem cell division one or both of the daughter cells can maintain the stem cell phenotype. Stem cells can divide symmetrically or asymmetrically. Explain each term.

During symmetric division both new cells acquire the same fate: both undifferentiated or both differentiated, whereas during asymmetric division you end up with one of each.

What are telomeres?

They are non-coding end portion of chromosome. Telomeres are non-coding repeating sequences on the ends of chromosomes. It protects the end of the chromosome from deterioration or fusion with neighboring chromosomes.

Normal human somatic cells have telomeres which are shortened by 50 - 200 base paire (bp) per cell replication.
What causes this shortening?

This shortening is the source of the "mitotic clock" and the Hayflick limit.(�50-70 doublings prior to replicative senescence.).

What happen when telomere length is shortened?

We know that Telomere length in humans is 9-11 kbp and when it reaches 5-7 kbp the chromosomes become unstable. Once chromosomes become unstable replication ceases or becomes prone to mutation.

What shortening of telomeres mean?

Shortening of telomeres means that the chromosomes become unstable which leads to cessation of replication it becomes prone to mutation.

When cells cannot differentiate there is no telemerase activity, that's when mitotic clock begin. True or false?

True.

How Telomeres can be repaired?

Telomeres can be repaired through the enzyme telomerase.
This enzyme is highly active in microorganisms such as yeast and cancer cells as well as embryonic stem cells.
To a lesser extent in adult stem cells.

Embryonic stem cells can divide indefinitely, but once they differentiate their mitotic clock begins. True or false?

True. Embryonic stem cells can divide indefinitely, but once they differentiate their mitotic clock begins.

Adult stem cells have finite limits of replication or a set number of replication, so they experience limited

self-renewal.Telomere shortening less pronounced than in differentiated cell types

In class, an integrated model that describes an aging stem cell system had been introduced. After how many doubling does senescence occur?

Senescence occurs after 90 doublings when telomere length is shortened to 6.5 kbp. Senescence is the property characteristic of old age.
Rate of telomere loss of 50 base pair (bp) per doubling.
Division results in a new but "older" stem cell.
Shortly afte

Major assumption during senescence.

The major assumption during senescence is that there is no difference in telomere loss between stem cells and committed cells.

What are cell lines?

Cell lines are unlike ordinary cells, which die after a certain number of divisions in culture; they are usually immortal cell lines established from tumor cells. Cell lines are cells with extended life-spans. They can be developed by transfection of the

True or false. Cell lines can be developed by transfection of the genes that code for telomerase.x

True. They can be developed by transfection of the genes that code for telomerase.

How cell lines can be developed by transfection of the genes that code for telomerase?

They can be developed by transfection of the genes that code for telomerase by:
hTERT - human telomerase reverse transcriptase
Can be retrovirally introduced into cells to extend their life or become "immortalized".
Cells will maintain the ability to prol

Stem cells are the starting material for many key processes in Stem cells must be considered an important source of regenerative potential both in vivo and for ex vivo cell culture processes. True or false?

True. Stem cells are the starting material for many key processes in Tissue Engineering and Regenerative Medicine. Stem cells must be considered an important source of regenerative potential both in vivo and for ex vivo cell culture processes.

Tissue Engineering is faced with reconstruction of two fundamentally different tissue types. What are they?

Connective tissue and epithelial tissue.

Bone marrow contains cells that can become both:

Connective tissue and epithelial tissue. While a single MSC capable of becoming all mesenchymal tissues has been isolated, there is not an equivalent epithelial stem cell.

Why do culture of adult stem cells in vitro requires appropriate cell microenvironments or niches?

Culture of adult stem cells in vitro requires appropriate cell microenvironments (niches) to promote proliferation without differentiation. For example,culture of Epithelial Stem cells in vitro requires a "feeder layer" of basement cells and a modified "c

what is a niche?

A niche is the range of physical and biological conditions in which a species lives and the way the species obtains what it needs to survive and reproduce.

Historically, stem cells have lost their differentiation and engraftment potential following in vitro culture. Therefore, it is important to improve our culture techniques and replication of stem cell microenvironments. How to do that?

We can do that by enhancing scaffolding, growth factors, signaling molecules, etc.

The fate of a stem cell not only depends on the genetics of the cell itself but also on epigenetic cues i.e. the signals it receives through its environment. True or false?

True. The fate of a stem cell not only depends on the genetics of the cell itself but also on epigenetic cues i.e. the signals it receives through its environment.

The fate of a stem cell not only depends on the genetics of the cell itself but also on epigenetic cues i.e. the signals it receives through its environment. True or false? Therefore, the interactions of exogenous signals with intracellular signaling mech

Quiescence
Self-renewal
Differentiation
Migration
Apoptosis

What is quiescence?

A state of dormancy

Chemical Signals of stem cell communication:

Cytokines and growth factors secreted , hormones, ions, Reactive oxygen species (ROS).

Physical forces of stem cell. List some of them

Cell shape, Matrix elasticity and topography, Tensile and compressive strains, Fluid shear stress, Gravitational forces, Electromagnetic fields,
Oxygen tension

Cellular things in Stem cells

Stem cell progeny, cell from other lineage, soluble factors

What Reactive oxygen species (ROS) at low levels can promote?

At low levels, Reactive oxygen species (ROS) can promote self-renewal of neural progenitors.

Physical forces can contribute to the formation of the niche and can originate from different sources such as the ECM. The ECM's contribution to the stem cell niche includes its physical properties, structural support, and its role as a reservoir of many

True. Physical forces can contribute to the formation of the niche and can originate from different sources such as the ECM. The ECM's contribution to the stem cell niche includes its physical properties, structural support, and its role as a reservoir of

Oxygen tension can be high or low. which one favors self-renewal of hematopoietic stem cells and endothelial differentiation of ES cells?

Low oxygen tension favors self-renewal of hematopoietic stem cells and endothelial differentiation of ES cells.

Cell differentiation capacities. Zygote are

totipotent

Cell differentiation capacities. Embryonic stem cells are

pluripotent

Cell differentiation capacities. Mesenchymal, Endodermal and ecdtodermal stem cells are

Multipotent

What are Induced pluripotent stem cells (iPSCs)?

iPS cells are are a type of pluripotent stem cell that can be generated directly from adult cells. They are differentiated cells which are reprogrammed and turned into pluripotent cells through transduction of genes encoding ES cell transcription factors.

Fibroblast and other adult somatic cells, classically used to have 4 factors delivered by retroviruses. The new method only have 3 which are:

Fully reprogrammed iPS cells
Partially reprogrammed iPS cells
Aberrantly reprogrammed iPS cells (refractory to differentiation)

Obstacles of iPS cells. Three obstacles became apparent:

Reprogramming efficiency: ~0.01 - 0.02%
Genome modification has the potential to produce tumorigenic insertional mutations.
Derivation and culture required the use of undefined human ESC

Stem cells are cells that can self-renew and produce differentiated daughter cells of more than one lineage. Stem cells can build tissues in vivo and are thus of fundamental importance to TE. Adult stem cells are not able to self-renew indefinitely and ma

True. Stem cells are cells that can self-renew and produce differentiated daughter cells of more than one lineage. Stem cells can build tissues in vivo and are thus of fundamental importance to TE. Adult stem cells are not able to self-renew indefinitely

MSCs are used daily in various clinical settings. ESCs are used mainly in a laboratory setting with significant governmental restrictions. iPSCs are in their infancy, and are used primarily for in vitro studies of biological processes and disease modeling

True MSCs are used daily in various clinical settings. ESCs are used mainly in a laboratory setting with significant governmental restrictions. iPSCs are in their infancy, and are used primarily for in vitro studies of biological processes and disease mod