• What are Stem Cells?
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The ASCC effort is an innovative approach to the use of stem cell technologies based on world-class expertise. Our programs have the potential to place Australia at the forefront of cell-based therapeutics and may be the first widespread use of a product based on human embryonic stem cell technologies

Over thirty years ago bone marrow transplants were the first clinical applications of adult stem cells. More recently, stem cell research came to the forefront of public awareness, with the announcement of the birth of Dolly the sheep the first cloned mammal in 1997 and subsequently the derivation of the first human embryonic
stem cells in 1998.

Stem Cells in the Laboratory

Since the discovery of adult stem cells they have been used to treat thousands of patients worldwide and continue to be studied in research institutes all over the world. More recently scientist has discovered additional adult stem cell types throughout the human body and the possibility that these resident adult stem cells can be used for applications in regenerative medicine and cell therapies. The jury is out on whether adult stem cells have the versatility and applications of embryonic stem cells – see Types of Stem Cells.

Human embryonic stem cells are derived from the blastocyst, a 4-7 days old embryo (see image below, taken with the microscope), of which the inner cell mass has been extracted and put into culture. Whereas embryonic germ cells are derived from the part of a human embryo or fetus that will ultimately produce eggs or sperm (gametes).This is called the gonadal ridge and is present at 6 to 9 weeks of gestation when the embryo is developing into a fetus – see Types of Stem Cells.

Once stem cells have been isolated they are transferred into a laboratory culture dish that contains a nutrient-rich culture medium. The inner surface of the dish is usually coated with a feeder layer of cells that have been treated so that they will not divide. These cells provide a sticky surface to which the cells from the embryo can attach, and also release nutrients into the culture medium. The stem cells then divide and spread over the surface of the dish. As these cells divide, some are removed to populate fresh subcultures (called passaging) to form a stem cell line.

Different stem cell types have shown varying abilities to be cultured in the laboratory. Embryonic stem have been shown to divide successfully over 200 times, thus deriving millions of embryonic stem cells. When Embryonic Stem cells have been grown in culture successfully for six months or more, without differentiating, they are referred to as an embryonic stem cell line. These embryonic stem cell lines are “immortal” because they have an unlimited capacity to keep dividing in culture. There are many new embryonic stem cell lines around the world.

Nationwide Resources Click image to view PDF (352kb)

Embryonic germ cells have been subcultured up to 70 to 80 times successfully. Adult stem cells have also been cultured in laboratory conditions. The differing ability to propagate new cells helps determine the best application for each cell type.

Once cell lines are established they can be frozen and shipped to other laboratories for further culture and experimentation. These stem cell lines can then be used in research to:

• identify what conditions and which factors are necessary to consistently induce stem cells to become specific cell types. If scientists can accurately direct their differentiation in the laboratory, these cells would be an unlimited source for transplantation cell therapies.
• investigate factors which control development and differentiation of the early embryo. The factors that lead to developmental abnormalities, such as cancers, can also be studied.
• screen drugs and possible toxins in vitro, before they are tested in animals and humans.

Under the right conditions Embryonic stem cells can remain undifferentiated for an indefinite period. However, they may spontaneously differentiate into specific cell types (eg nerve cells) if they are left to form unattached clumps in the culture dish. These clumps are called embryoid bodies and can further differentiate into a mixture of cell types. Scientists are working to control the differentiation of stem cells into specific cell types. A number of ways to do this include:

• adding certain growth factors to the culture medium,
• changing the surface properties of the culture dish,
• co-culture with other cells such as mouse feeder cells
• co-culture within a supportive scaffolding or matrix
• or by activating the cells with their own (endogenous) control molecules called transcription factors.

As scientists learn how to direct the differentiation of stem cells into specific cell types, they will be able to use these cells to treat specific diseases such as Parkinson’s disease, diabetes and heart disease.

World View

Researchers around the world are focusing on investigating the molecular and developmental characteristics of all stem cell types and improving the culture methods such as growing cells without using animal products. These animal products may be a source of viruses and harmful molecules called prions that may limit or preclude the use of the cells for transplantation.

Scientists are now beginning to have success in making stem cells differentiate into particular types of cells and to identify whether these specialised cells function normally. Australian scientists have been at the forefront of this research. Scientists in Australia have also been working on using adult stem cells in cell-based therapies to treat conditions such as heart disease. They are also looking at whether stem cells could be seeded into scaffoldings or matrices to create a complex organ.

In 2000, a group of scientists led by Professor Alan Trounson, from the Monash Institute of Reproduction and Development, first reported nerve stem cells derived from embryonic stem cells. This discovery was reported on the front page of the scientific journal Nature, which is the science equivalent to having your photo on the cover of the Rolling Stone!

Australian Stem Cell Centre

Today, much of the research in Australia on stem cells is directed through the Australian Stem Cell Centre, a Biotechnology Centre of Excellence established by the Federal Government in 2003. This centre brings together stem cell researchers from around Australia.

The Law and Stem Cell Research in Australia

Laws which regulate stem cell research differ markedly from country to country. There is particular variation in the ethical values and hence the laws governing embryonic stem cell use and derivation.

In Australia, there is a piece of legislation covering stem cell research and cloning. This is the Regulation of Human Embryo Research Amendment Act 2006.

The various States and Territories of Australia have their own legislation regulating the use of embryos in research, which seeks to be consistent with the Commonwealth legislation.

There is no legislative framework regulating the use of human stem cells (embryonic or adult) after they have been derived. However, the use of human stem cell lines in research must comply with relevant National Health and Medical Research Council (NH&MRC) guidelines.

When using human embryos for research, scientists must obtain a licence from the NH&MRC.

The Therapeutic Goods Administration in Australia is developing a national regulatory framework for human tissues and emerging biological therapies.

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