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What are Stem Cells?

What are Stem Cells?
Stem Cell research at the McEwen Centre

What are stem cells?

Stem cells are undifferentiated (or unspecialized) cells that are capable of renewing themselves indefinitely. This undifferentiated state means that a single stem cell has a unique capability to grow and generate a wide variety of specialized cell types (for example muscle cells, neurons, heart muscle cells, etc) under the right physiological conditions.

The tremendous therapeutic potential of stem cells lies in their remarkable potential to generate a variety of specialized cell types. If stem cells can be grown in the laboratory and coaxed into producing various types of specialized cells, they could provide a renewable and virtually unlimited source of cells to repair or replace damaged or diseased cells and tissues.

Embryonic Stem Cells

Embryonic stem cells are derived from a very early stage embryo known as a “blastocyst,” a cluster of cells which resembles a hollow, micrsocopic sphere. Unlike adult stem cells, which are restricted to producing limited cell types, embryonic stem cells have the potential to generate every cell type in the body.

Embryonic stem cells can be grown in culture indefinitely and thus generate a very large number of cells. They are the most versatile type of stem cells and under the proper conditions, they have the potential to generate all types of cells in the body. Tremendous research efforts are currently underway to determine the right conditions to produce specific cell types for cell replacement therapies.

Stem Cells from Adult Tissues

Many different adult tissues have been found to contain stem cells which are thought to play an important role in maintaining and repairing specialized cells and tissues. For decades, bone marrow has been known to contain blood-forming stem cells. Stem cells have now been uncovered from adult tissues as diverse as skin, hair follicles, blood vessels, liver, the digestive tract and the nervous system. They can have different properties depending on their tissue or organ of origin, but are less flexible than embryonic stem cells: generally, they only produce the type of cells found in their tissue or organ of origin.

Current research focuses on understanding how adult stem cell differentiate into specialized cells and developing techniques to effectively produce large amounts of adult stem cells. Adult stem cells could become an ideal source of cells for replacement therapies since they could be obtained from the patients themselves, avoiding problems associated with rejection.

Hematopoietic stem cells are a type of adult stem cells found in the bone marrow. In normal conditions, they continuously produce new blood cells and immune cells. They are relatively easy to obtain and have been used in medical treatments for over 30 years–for example to treat patients with leukemia.

Umbilical cord blood stem cells are a type of hematopoietic stem cell that can be obtained from the umbilical cord of newborns. Unlike embryonic stem cells, they cannot be grown in culture indefinitely. However, the umbilical cord represents an easily accessible and abundant source of hematopoietic stem cells.

Stem Cell Research at the McEwen Centre

• Dr. John Dick has gained international recognition for his lab’s work on cancer stem cells and for the development of the NOD/SCID mouse, an experimental model that transformed the study of both normal and leukemic human blood systems.

• Dr. Norman Iscove is studying the genes and mechanisms involved in the self-renewal and differentiation of hematopoietic stem cells in normal and leukemic systems. In other words: when a blood stem cell divides, what are the factors determining whether it will make a copy of itself or become any one of the various types of cells present in the blood? One of the goals of his research is to identify key genes responsible for the maintenance and extinction human leukemia cells – such genes could be of high therapeutic potential.

• Dr. Gordon Keller’s expertise lies in embryonic stem (ES) cell differentiation. His team is studying the mechanisms that regulate the development of ES cells into specific lineages and cell types – many of which (for example, heart cells or pancreatic beta islet cells) have great therapeutic potential.

• Dr. Freda Miller is studying the differentiation and survival of developing and injured neuronal cells. Her group has discovered that mammalian skin contains a type of stem cells that can be isolated and that can generate various types of cells including smooth muscle and neural cells. This major discovery opens possibilities for a new source of readily accessible cells that may be used for therapeutic purposes.

Figure: Skin-Derived Precursors (SKD) – a type of stem cells located in the deep layers of the skin which was discovered in Dr. Miller’s lab. Credit: Miller lab

• Dr. Andras Nagy’s research involves the use of ES cells as a genetic model for the mouse and the study of self-renewal and early differentiation in embryonic stem cells. His group is also investigating blood vessel development in normal and diseased conditions.

• Dr. Derek van der Kooy’s areas of focus is neural stem cells, both in the early stages of development of the mammalian brain and in the adult brain – where neural stem cells can still produce new neurons and glia. His group is testing the ability of these new cells to re-establish function in animal models of human neurological disorders. Other areas of interest include retinal and pancreatic stem cells.

Figure: Human retinal stem cells transplanted into a developing mouse eye can integrate and differentiate into both photoreceptor and retinal pigmented epithelial cell types after 30 day survival in vivo. Credit: van der Kooy lab. From Coles et al., PNAS 2004;101(44):15772-7.

• Dr. Peter Zandstra is investigating the molecular mechanisms governing the fate of embryonic stem cells (self-renewal vs differentiation). His group is developing “bioreactors” specially designed to provide stem cells with optimal growth conditions. Developing cost-efficient methods to produce stem cells at a larger scale is essential for both basic research and - at later stages - for the clinical application of stem cell technologies.

Figure: Stereoscopic projection of a stem cell dividing within a group of cells. The cells are stained with dye that labels DNA. Several nuclei are visible, and in the center of the image, two bundles of chromosomes can be seen pulling apart as the cell divides. To get the full 3d effect, cross your eyes and overlay the image - holding a piece of paper up between the image halves (so each eye can only see one image) may help. Source: Zandstra lab