Stem Cells and Embryonic Development · Example of embryonic stem cell-based therapy Note that embryonic stem cells cannot be transplanted “as-is” for therapies. If you inject

Stem Cells and Embryonic Development

How old is this?

What is it?

What is this?

How old is it?

© Mark Hill, UNSW

Central ethical question surrounding embryonic stem cell

research:

Under what circumstances, if any, can 5-14 day old human embryos be:

1. Created and destroyed (prevented from developing further, then immortalized) for research purposes?

2. Donated as research material as a result of the In Vitro Fertilization procedure?

3. Checked and screened for certain genes then selected for or against?

Outline of Presentation

• Natural Fertilization

• In vitro fertilization

• Embryonic development

• Where are embryonic stem cells found?

• What are the other types of stem cells?

• How do CIRM scientists use embryonic SCs?

• Can and should we select for genetic makeup?

Natural Fertilization

The “Old Fashioned Way”

+ =









In the IVF procedure, sperm and eggs “interact” in a dish leading to insemination.

They literally swim up to the egg and burrow toward the nucleus.

The first one to get there wins, and all others are blocked out.

Male fertility issue: Sometimes sperm cannot latch onto and penetrate the egg.

They may choose to have Intra(within)-Cytoplasmic Sperm Injection (ICSI)

Day 1

These procedures happen in a dish, or in vitro. From here, regular In Vitro

Fertilization and ICSI are the same. This is also how the fertilized egg looks in

the woman’s body on day 1 after conception.

As early as 12 hours after fertilization you can see the two bundles of genetic

material, one from each parent. These are called pronuclei. By 18-20 hours

after fertilization, these pronuclei fuse, combining genetic material from mom

and dad.

What starts out as two cells becomes one cell, called the fertilized egg or

zygote.

On day 2, that one cell we called the zygote has divided into two cells. How are

they related to each other?

Later on day 2, each of those two cells divides, making four identical cells.

day 3, each of those four cells divides, making eight identical cells. Each

cell is one-eighth the size of the original zygote.

Some in vitro fertilization clinics choose to implant the embryos back into

the uterus at this stage, and some wait until the embryo is more

developed.

On day 4, the cells have divided several times more and are indistinct. How do you

think these cells relate to each other?

Embryonic

Stem

Cells

Day 5: Fluid builds up inside the ball of cells, making it look hollow like a soccer ball.

This structure is called a blastocyst. Are the cells here still identical? No, they are

not.. The outer layer of the blastocyst is made up of cells that are destined to

become the placenta. There is a clump of cells sitting inside the blastocyst, that is

destined to become the fetus. However, this is definitely not a fetus yet.

Now, the in vitro fertilization doctor chooses a few, usually 2-3, healthy-looking 5-

day-old blastocysts out of the batch of 10-30 blastocysts—from the 10-30 harvested

eggs—and implants those into the woman’s uterus. Hopefully one, and preferably

only one of those will successfully burrow into the uterine lining and continue

developing into a pregnancy.









Embryonic Development: Fish model

Keller et al. 2008

At what point is it a fetus?

• Days 7-14: Uterine implantation

• Day 14: Three distinct layers begin to form (no more pluripotent stem cells)

• Days 14-21: Beginning of future nervous system

• Days 21-24: Beginning of future face, neck, mouth, and nose

• Weeks 3-8: Beginning of organ formation This picture is Week 5

• Week 5-8+: Now it’s called a fetus (no consensus on a single timepoint)









This cell

Can form the

entire human being

This cell

Cannot form the

entire human being

Fully mature

Symmetric cell division

Asymmetric cell division

1. Self-renews

2. Differentiates

Progenitor cell

Stem cell Stem cell









What is stem cell research?

• Understand more about development, aging, disease

– Experimental model systems

• Prevent or treat diseases and injuries

– Cell-based therapies

– Pharmaceutical development

• Includes testing and drug delivery

Spinal cord injury: Example of embryonic stem cell-based therapy

Note that embryonic stem cells cannot be transplanted “as-is” for therapies. If you inject

embryonic stem cells into a patient, those cells often turn into nasty tumors called

teratomas. Teratomas contain many differentiated tissues because the extracellular

environment has given them abnormal differentiation instructions. In order to be used for

therapies, embryonic stem cells must first be coaxed to differentiate into adult stem cells,

progenitor cells, or fully mature cells.

CIRM funding breakdown: Cell Type

CIRM funds many types of Stem Cell Research









Pre-implantation Genetic Diagnosis • A procedure to see if the baby has a chance of

inheriting genetic diseases

• One-two test cells taken from morula stage

• The embryo can grow normally if chosen for implantation

• Two techniques:

– Heteroduplex Analysis: DNA is tested for structural abnormalities

– Fluorescence In Situ Hybridization (FISH): Chromosomes are dyed to look for translocations and check the number of chromosomes

Ethics of Pre-implantation Genetic Diagnosis

• If the embryo shows a genetic variation linked with a genetic disease the parents could decide to terminate that pregnancy or not use that embryo

Discuss:

Under what circumstances, if any, can 5-14 day old human embryos be:

1.Created and destroyed (prevented from developing further, then immortalized) for research purposes?

2.Donated as research material as a result of the In Vitro Fertilization procedure?

3.Checked and screened for certain genes then selected for or against?

Documents

Stem Cells and Embryonic Development · Example of embryonic stem cell-based therapy Note that embryonic stem cells cannot be transplanted “as-is” for therapies. If you inject