1. Introduction to Stem Cells
Prepared by the
AUSTRALIAN STEM CELL CENTRE
         
This presentation has been compiled based on feedback we have received from teachers and students involved in last 2009’s Back to Schools program.
You are welcome to modify as you see fit.
Note that it was requested that the presentation be interactive - suggested interactive slides are designed as builds and include: #2, 10,11 and 12.
     

2. Introducing….stem cells!
This slide is designed to be interactive.
Start with a question like “What do you think of when someone mentions stem cells?” and allow the students to suggest key words.
At the click of a mouse in will come key words associated with stem cell research. 2

3. What are stem cells?
the body is made up of about 200 different kinds of specialised cells such as muscle cells, nerve cells, fat cells and skin cells
all cells in the body come from stem cells
a stem cell is a cell that is not yet specialised
the process of specialisation is called differentiation
once the differentiation pathway of a stem cell has been decided, it can no longer become another type of cell on its own
This slide introduces some basic terms and concepts about stem cells. 3

4. Embryonic stem cells (pluripotent) Tissue stem cells (multipotent)
Why are stem cells special?
Stem cells can:
self-renew to make more stem cells
differentiate into a specialised cell type
Embryonic stem cells (pluripotent)
Stem cells that can become many types of cells in the body are called pluripotent
Tissue stem cells (multipotent)
Stem cells that can become only a few types of cells are called multipotent
This slide explains the basic properties of stem cells and introduces the concept of classification based on potency.

5. Tissue stem cells often known as adult stem cells
also includes stem cells isolated from fetal and cord blood
reside in most tissues of the body where they are involved in repair and replacement
Bone marrow
Kidney
Lung
This slide provides key information about tissue stem cells.
Other points you may wish to raise are:
tissue stem cells are multipotent, meaning they only give rise to a limited number of different tissues
under the right conditions tissue stem cells can be grown in the laboratory
tissue stem cell are widely use in research
treatments based on tissue stem cells are limited to blood cancers like leukeamia and auto-immune diseases (and have been for over 50 years). These treatments involve stem cells obtained from bone marrow and umbilical cord blood
there are many other therapeutic applications of tissue stem cells currently being evaluated but these are not yet clinically proven and widely accepted. For example, clinical trials are underway to use adult stem cells to treat long bone fractures, kidney failure, heart failure, arthritis and cartilage regeneration, just to name a few possible future applications
the use of tissue stem cells in research and in the clinic attracts less controversy than other types of stem cells (eg ES cells) but still require ethics approval to create and use in the laboratory and the clinic.
generally very difficult to isolate
already used to treat patients (haematological malignancies, diseases of the immune system) 5

6. Where do embryonic stem cells come from?
Donated excess IVF embryos
Inner cell mass
egg
fertilised egg
2-cell
8-cell
blastocyst
This slide provides an overview of embryo development during IVF. To understand where embryonic stem cells come from it is helpful to introduce how embryos are made.
Other points you may wish to raise are:
At the completion of their infertility treatment, IVF couples must decide what happens to any embryos they may still have frozen. Not all couples will have excess embryos. Their options are to discard the embryo (disposed of in biological waste), donate the embryo to research, or donate their embryo/s to another couple. Couples decide what to do and are not forced to donate their embryos if they don’t want to
Concept of early cell division from fertilised egg (PN visible in D1 image) through to formation of blastocyst approximately one week after fertilisation
Blastocyst has two different cell types – inner cell mass and trophectoderm (ICM highlighted by red oval). These cell types has different function with ICM generating all the cells of the body
ES cells are made by isolating the ICM and growing it in the laboratory
It has been legal to use human embryos in research in Australia since 2002 when specific legislation was passed Research Involving Human Embryos Act Any researcher wanting to use embryos in their research must obtain a licence from the government specifically for their project
Human embryos have been used in research to improve infertility treatment and to make embryonic stem cells.
Day 0
Day 1
Day 2
Day 3
Day 6
Images from 6

7. human embryonic stem cells
derived from donated IVF embryos
can be grown indefinitely in the laboratory in an unspecialised state
retain ability to specialise into many different tissue types – know as pluripotent
can restore function in animal models following transplantation
human embryonic stem cells
This slide introduces key facts about embryonic stem cells.
The first image is of a blastocyst ( cells but very small – 10 can fit on the head of a pin).
Embryonic stem (ES) cells are isolated from the inner cell mass of the blastocyst. The red oval highlights the inner cell mass (ICM)
Other points you may wish to raise are:
differentiation is controlled/manipulated in culture and ES cells can differentiate into many different types of cells such as:
nerves including motor neurons
blood (haematopoietic) stem cells
insulin producing cells
liver cells (hepatocytes)
bone forming cells
Embryonic stem cells may provide a new way of studying diseases by making patient - or disease - specific stem cell lines. These can then be used to test drugs and treatments
Potentially, embryonic stem cells can be used to replace or restore damaged tissue, as with the proposed Geron trial in patients with acute spinal cord injury in the USA, however there remains significant hurdles to clinical translation such as the potential to form tumours and what stage of a cells differentiation is the most appropriate to deliver to a patient.
Human embryonic stem cells can become any cell in the body including these beating heart cells

8. Dolly the Sheep Snuppy the Puppy
What about cloning? Has that got anything to do with stem cell research?
Somatic Cell Nuclear Transfer – cloning to make stem cells (therapeutic cloning)
Dolly the Sheep
Reproductive Cloning
Snuppy the Puppy
Human cloning is banned in Australia and many countries around the world.
This slide explains cloning technology and aims the delinate between SCNT (otherwise known as therapeutic cloning) and reproductive cloning.
Start with the question on the slide, and see what the response is and then discuss the following points.
The first image describes the process used to make stem cells from SCNT embryo:
take an egg, remove its nucleus - the DNA – and add a new nucleus of a cell from the animal to be cloned
the reconstructed egg is then treated with chemicals or an electric jolt to start cell division and placed in a dish of nurturing chemicals to make it divide
a few days later it becomes a cluster of cells call a blastocyst
to make stem cells, the inner cell mass is isolated and grown in the laboratory
these stem cells could theoreticaly be used to study disease, used in drug discovery or in new therapies
HUMAN STEM CELLS ARE YET TO BE ISOLATED USING THIS APPROACH
However, it has been legal since 2006 to make human embryos using SCNT provided a license is obtained from the government - Prohibition of Human Cloning for Reproduction and the Regulation of Human Embryo Research Amendment Act 2006
Reproductive cloning also uses the same technique to make the embryo BUT instead of keeping the embryo in the laboratory, the embryo is placed into a surrogate. This is how Dolly the sheep was made and Snuppy the Puppy. Although some groups want to use this technology to CLONE humans (like the Raelin movement which believe that humans were brought here by spaceships and that human cloning is the first step to immortality, the Raelien leader is shown in picture), the reality is that human cloning is banned in most countries in the world and has been in Australia since Prohibition of Human Cloning Act Any who breaks this law faces 15 years in jail!
In 2006 the legislation was amended to allow therapeutic cloning with the passage of the Prohibition of Human Cloning for Reproduction and the Regulation of
Human Embryo Research Amendment Act 2006.

9. Induced pluripotent stem cells
Starting cells from donor tissue
derived from adult cells in very recent discovery!
can be grown indefinitely in culture in an undifferentiated state
similar properties to embryonic stem cells as can differentiate into many different tissue types –pluripotent
can create stem cells directly from a patient for research
Induced change in gene expression
iPS Cells
This slides aims to introduce induced pluripotent stem (iPS) cells.
Points you may wish to raise are:
In November 2007, scientists announced they had developed a new technology to induce mature human cells to revert back to a more primitive or undifferentiated state
iPS cells are pluripotent and share many similarities with human embryonic stem cells (ES cells)
The techniques used to induce or reprogramming the mature cells involves a change in the pattern of genes expressed which is often triggered by inserting certain genes involved in early development (genetic modification)
You might want to include more detail on the techniques used to generate iPS cells (use of viruses, transcription factor driven, retention of donor origin ie epigenetic memory)
fewer perceived ethical/legal problems because creation of iPS cells does not require the destruction of embryos
iPS cells can be grown in large numbers and used to create disease - or patient - specific stem cell lines but many questions remain to be explored about iPS cells before they can be used in the clinic:
- are they really equivalent to human embryonic stem cells?
- are they stable over a long time?
- will they be safe and effective for treatment?
pluripotent stem cells

10. Using stem cells to conduct medical research and treat disease is acceptable?
Don’t know No
Yes 3% 5%
92*%
Biotechnology Australia – Community Attitudes to Biotechnology (2007)
* Compares to 80% in 2005 survey
The aim of this slide is to make students aware that not everyone in the community supports stem cell research and start to challenge them to share/form an opinion.
You could start by asking the students what they think about stem cell research, then what they think the community thinks, then show the results from the 2007 survey. Note that there was a increase in community acceptance from that observed in an earlier survey conducted in 2005.
The limitation of this question is that it doesn’t specify what type of stem cells. You can ask the student if you think the results would change when different types of stem cells are proposed to be used in research. Then show the following slide to indicate the level of acceptance in the community around the use of human embryos for stem cell research.
But which type of stem cells?
pluripotent stem cells (embryonic, SCNT, iPS stem cells)
tissue stem cells (foetal, cord, adult)

11. Do you approve of the extraction of stem cells from human embryos for medical research?
Roy Morgan Poll (2006) 5%
13%
82%
Don’t know No
Yes
If you ask a more specific question about embryonic stem cells, what is the class response, do they think answer will differ from the generic question and again how does it compare with the poll results.

12. Areas of community concern
How come there are excess IVF embryos?
Why do the embryos have to be destroyed for stem cell research? Isn’t this the same as taking a life?
Wouldn’t it be better to donate the excess IVF embryos to other infertile couples?
Could women be forced to sell eggs or embryos for research?
Won’t doing therapeutic cloning lead to cloning humans?
Why do we need to keep using embryos in research when we have new iPS cells?
Ask the class what they think the community is concerned about when it comes to stem cell research.
We have suggested some issues that are frequently raised about stem cell research and would suggest once you have canvassed the student’s opinion, you could share these points and discuss.
Key point here is that Australia has stringent legislation that addresses many of these concerns. However, some members of the community will always object to the creation of human embryos and any research use because they believe that a human embryo is equivalent of a life.
Other members of the community recognise that human embryos have the POTENTIAL to be a life but are not yet a life (raises question of when does life begin).
When it comes to IVF, doctors can’t predict how a women will respond to infertility treatment and as a result can’t produce the exact number of embryos required for them to complete their families. As a result, sometimes couples have embryos left over once they have completed their families. These embryos are usually frozen in liquid nitrogen. The couple has to freely decide what happens with these embryos and provide written consent of their desire. The options are that they can donate their embryos to research (which includes infertility treatment and stem cell derivation), donate their embryos to another couple (akin to adoption and a difficult decision) OR discard their embryos. All of these choices are difficult but some couples would prefer to see their embryos donated to research rather than thrown away.
Australian legislation specifically prohibits the sale of eggs and embryos AND the coercion of couples or women to donate their eggs or embryos.
Australian legislation also specifically prohibits anyone trying to clone a human using SCNT or other cloning technology.
The last question is attempting to highlight that we still have much to learn about iPS cells and that it is too early to abandon other areas of research.
Australia has clear rules that allow embryos to be used in research under strict conditions.
All research whether it involved embryonic, adult, cord, fetal, iPS stem cells must have special ethics approval before research can start.

13. What makes stem cells so valuable?
Cell Therapy
Pluripotent stem cells
Tissue stem cells
Research
New Drugs
This slide summarises where stem cells are used and can be used to highlight that we are already using stem cells in research to identify new drugs, provides a unique supply of cells for drug screening as well as attempting to advance to cell therapy to treat currently incurable conditions with replacement cells.
The challenges for stem cell therapy and regenerative medicine are:
production of required cell type in sufficient numbers and pure form
what cells to transplant
how to deliver the cells
other safety issues
problems of tissue rejection
Modified from Keller & Snodgrass, Nat Med 1999
No one stem cell type fits all applications.
Research must continue using all types of stem cells. 13

14. Stem Cell Tourism
A growing concern to the stem cell community
Direct marketing to patients promising instant results for incurable diseases
This final slide addresses the issue of stem cell tourism where some overseas clinics are offering unproven and experimental treatments to patients suffering from a vast array of conditions at a very high cost without any proof of effectiveness or even safety!
The Australian Stem Cell Centre receives an enquiry, on average, every day from someone regarding unregulated overseas experimental stem cell treatment.
Australians need to be cautious before embarking on such treatments and make sure they discuss their options fully with their treating doctor.
More information on this topic is available in the ASCC Patient Handbook. 14