18: CBIO Stem Cells

What are fertilized eggs

produces clones

(totipotent) - can make fully formed, multicellular complex ogranisms

• cells divide over adn over again to get a varitey of cells for the body

Requirements of tissues

1. mech stengrh (CT)

2. delivery of O and nutreints (blood vessels)

3. removal of waste

4. disposal of dead and damaged cells

5. combat infection

significant fact about cells examples

• orginate outside of tissue and then invade it (made whre they dont belong)

• during development like: nerve cell axons, endothelial cells, schwann cells’

• coninously macro and other blood cells

What does stability of tissue mean

1. mixture of diff cell types need to be diff

2. dead or damaged cells always needed to be replaced

factors of tissue stability

1. cell communication - monitors and reacts to signals

2. selective cell adhesion - homophilic binding (binds to simliar) and selective binding to keep cells in the right place

3. Cell memmory - cells keep their identiy and pass it to progeny

Explain tissue renewal rates

Can go slow and fast renewal depending on the cell type

• intestinal cell s3-6 days

• nervouse tissues - dont divide

how does bone renewal work

osteoclasts - slowly eats away old bone matrix

osteoblasts - deposit new matrix

where are blood cells made? and removed after how many days? what about skin? what does ionizing radiation do?

bone marrow

removed until 120 days

skin renewal is 2 months

• blocks cell dividison and stops tissue renewal so bones become brittle

what are terminally differntiated cells? examples

• has their own function, but CANT DIVIDE SO DEADEND

cells needed to be replicated but cant divide themselves

1. rbc - come from bone marrow then transported into blood vessels

2. epidermal cells in the upper layer of skins

3. linings of gut epithelium

• does not go thru replicatoin so we have stem cells that replace it in our body

what can these terminally diff cells do if they cant divide themselves? what can daughter cell sbe

• replaced by proliferating precursor cells which come from self renwing stem cells

  • CONTINUOUSLY DIVIDE and NOT differentiated

• daughter cells can remain a stem cell (undiff that can divide into a specialized cell, immature cell) or terminally diff

diff between stem cells and precurosr cells? where are stem cells located

stem cells - can divide into MANY speicialzied cells

precurosr - not a lot divded into

• remain in their resident tissues along w their undiffeentiated progeny

What are stem cells?

1. small numbers

2. difficult to describe and find in tissues using molecular markers

• so we identify them by proteins cell surface, staining,

3, Developmentally restricted

• expresses transceipriton regulators (can be turned on or off)

• Ensure differentiated progeny will be the appropriate cell types

• produces only the correct, SPECIFIC functional cells needed for that particular tissue (a blood stem cell only makes blood cells, not skin cells)

4. one type of stem cell gives several types of diff progeny

• ex. hematopoiesis (hematop wi sis)

  • hematopoeitic stem cell found in bone marrow and can give rise to rbc, platelets, and a lot of wbc versions

What is the lining of the sm. int? how does cell replacement occur

• single layer of absoprtive and secretory cells

1. stem cells at the bottom of the crypts give rise to proliferating precursor cells

2. Precursor cells move upward in the epithelial sheet

• turning into terminally diff into absorptive or secretory cells ( so it doesnt keep divding further)

3. diff cells die when they reach the tip of the villi and shed into the lumen of the gut

What are crypts?

epitheial tissue descending into the underlying CT

explain the cell replacement of epidermis

occurs in stratified epithelium (layers of cells in skin)

1. proliferating stem cells and precursor cells are stuck to the basal lamina

2. differentiating cells travel outward away from their origin (perpendicular to cell sheet)

3. then terminally diff cells and dead cells are shed from the skin surface when it reaches top

What are stem cell control mechanisms

• New differentiated cells must be made in the correct location and quantity

  • not alone, they communicate w neighbouring cells to decide when to divide and what to become.

what journey do stem cells go thru

stem cells -? pre cursor cells → terminall differentatied cells

What are Wnt proteins

• promote proliferation of stem cells and precursor cells in the intestinal crypt

• crypt cells secrete signals to prevent activation of Wnt pathways outside the crypt

  • so it doesnt allow division

• crypt cells exchange signals to control cell diversificaiton

  • basically controlling “we want more of this”

Whats unique about stem cells?

they can keep self-renewing all the time and produce progeny that diff (make a variety thats matured or spicalized), which allows the renewal of tissues

ex. mouse

• destroyed their dematopoietic stem cells and tranfused a donor one and the animal was able to repopulate new blood cells

ex. humans w leukemia (cancer of blood)

• irradiates the cancerous blood then give them bone marrow transplantation to make new hematopoeitc cells

What are embyronic stem cells (ES Cells)

1. pluripotent - can divide a bunch, while retaining its unrestricted diff (become any cell type in the body)

2. when introduced to a tissue, their progeny cells integrate and adopt the characteristics and behaviors of the normal cells surrounding them

• ES can make macro and travel to wbc and acct like it

3. can study gene function and development of mice

• can gnetically modify (inactivae or modify genes)

• uses signaling molecules to see how they differeintate (specliazed turn intO

What are human embyronic stem cells? whats wrong with it?

• potentially inexhuastible supply of cells that can replace or repair damaged tissues

1. immune rejection - immune system will destory the transplanted cells if genetically diff

2. Ethical consideration - we use human embryos to produce human ES cells…

What is induced pluripotent stem cells (iPS) ? whats it important for?

• taking differentiate cells from an adult human and reprogramming it to an embryonic state like

• the development of techniques for producing and directing human induced pluripotent stem cells via cell based therapies

  • treats muscular dystrophy by creating skeletal muscle fibers.

  • treats parkinson’s disease by creating nerve cells

  • treats type I diabetics by creating insulin

  • treats heart attack patients by creating cardiac muscles

how are induced pluripotent stem cells (iPS) reprogrammed to be embryonic state like?

1. Scientists force the expression of three transcription factors: Oct4, Sox2, and Klf4

2. These factors converts fibroblasts into cells with properties of ES cells.

3. Mouse cells successfully shown to form any tissue when tested in organisms, confirming their pluripotency

What is the current use of human induced pluripotent stem cells

1. generates large homogenous populations of diff human cells (heart cells)

• the specialized cells can be used to test potential toxic or beneficial effects of drugs

2. By creating iPS cells from patients with genetic diseases

a. produce affected differentiated cells that can be studied

• allowing reserachers to learn more about the disease mechanism and search for potential treatments

What are organoids? how are they formed? they resemble? ex?

• small organs grown in the lab

• ES cells and iPS cells forced to diff and self assemble to form^

• resemble the organization of normal organs

ex. Human ES forms an eye like structure

• so a multilayered retina similar to a developing eye

What have they’ve done so far w organoids?

formed organoids via mouse and humasn that resemble many organgs

• ex. huhman brain the most complex theyve produced

roles of organoids?

Studying organ development
• Identify and manipulate genes
• Explore cell-to-cell interactions
• How are developmental pathways derailed by disease