The Basics of Stem Cells

What are stem cells?

As you may know, our bodies consist of small organic entities known as cells. We have millions of them! There are many different types of cells, each having different shapes, sizes, and functions. One feature is common amongst all cells, however: all cells come from other cells which already existed. So you might ask: If all cells come from other cells, which cells do all cells come from in the beginning? The answer is stem cells.

According to the National Institutes of Health "Resource for Stem Cell Research", stem cells are cells that have a remarkable potential to develop into many different types of cells in the body, during early life and growth. Stem cells were first specifically identified by Russian-American scientist Alexander Maximow in the early 1900s.  (Citation 7) (Citation 2)

In the following sections, you will learn more about what makes stem cells unique, how they function, different types of stem cells, and challenges in stem cell science.

A diagram showing the some of the basic key characteristics of stem cells. Stem cells differ from normal cells in that they have multipotential (ability to turn into several different types of cells), have an ability of self-renewal, and are highly proliferative. (Image made by website author)

What makes stem cells unique?

So, why are stem cells different from other cells? Why do scientists and clinical researchers use stem cells and not other cells? Well, stem cells have three key characteristics which make them very useful for medical research.

1. Multipotential: Stem cells have the potential to turn into many different types of cells (a process called differentiation). For example, while your skin cells can divide to form only other skin cells, mesenchymal stem cells (a special type of stem cell) can differentiate into bone, cartilage, or fat cells. Embryonic stem cells can differentiate into more than 200 different types of cells.
2. Self-renewal: Stem cells can not only turn into other cells but also make more of themselves. This is very important for stem cells - otherwise, the body would run out of them very quickly!
3. Highly-proliferative: Stem cells have the power to make very large quantities of themselves (a process called proliferation) in a relatively short amount of time, allowing them to differentiate throughout the body whenever needed.

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Embryonic Stem Cells

Embryonic stem cells are derived from early embryos called blastocysts (which are approximately 150 cells). First derived by researchers from the University of Cambridge in mice, embryonic stem cells are pluripotent cells, which means that they have the ability to differentiate into any cells of the three germ layers.

Human embryonic stem cells (or hESCs) used for research in the United States are obtained from federally approved stem cell lines.

Embryonic stem cells are grown in laboratories by the use of cell cultures. A feeder layer of mouse embryonic stem cells provides essential nutrients to these growing cells. When induced, embryonic stem cells can differentiate into more than 200 different types of cells, making them extremely versatile for research purposes!

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Adult Stem Cells

Adult stem cells, also known as somatic stem cells, are undifferentiated cells found in matured tissues. While they can be used to develop cures and treatments, they cannot be used very extensively due to limitations in differentation potentials.

Some of the several types of adult stem cells include:

• Mesenchymal Stem Cells - Mesenchymal stem cells, also known as MSC, can differentiate into either bone cells (osteocytes), cartilage cells (chondrocytes) or fat cells. (adipocytes)
• Neural Stem Cells - Neural stem cells can differentiate into astrocytes (glial cells in the brain and spinal cord), oligodendrocytes (neuroglia or brain cells), or nerve cells, also known as neurons.
• Hematopoietic Stem Cells - Hematopoietic stem cells are found all throughout the body. They can differentiate into many different cell types, including red blood cells, natural killer (NK) cells, white blood cells (neutrophils, basophils, eosinophils), T lymphocytes, monocytes, etc.

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Stem cells already differentiated into neural cells. Some of these neural stem cells can be used as potential therapeutics for neurodegenerative diseases, such as Parkinson's Disease or Multiple Scleriosis. (Image Citation 14)

Induced Pluripotent Stem Cells (iPSCs)

Induced Pluripotent Stem Cells, or iPSCs, are one of the most innovative types of stem cells used in research. iPSCs were created in 2007 by two different groups (James Thompson at the University of Wisconsin-Madison and Shinya Yamanaka at Kyoto University in Japan) by reprogramming adult somatic cells into a pluripotent state, by the use of four different DNA-transcription factors. The DNA-transcription factors are called Oct3/4, Sox2, Klf4, and c-Myc respectively. All are highy expressed in embryonic stem cells.  In an essence, adult stem cells are induced to behave like pluripotent stem cells (such as embryonic stem cells) when the four factors are integrated into the adult stem cell's genome!

Researchers have since shown that iPSCs can be made from a variety of adult cells. iPSCs do currently have limitations for research use. The factors are inserted through the use of viruses (through a process known as transduction) which may be mutagenic and cause activation of unwanted genes. In addition, it is not known whether iPSCs have the exact same properties which embryonic stem cells have. However, iPSC research is rapidly leading to more conclusive data which supports the use of these innovative stem cells as therapeutic agents for combating disease.  

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Cancer Stem Cells 

Until recently, cancer stem cells (CSCs) were simply a hypothesis. However, now, scientists continue to confirm the existence of these cells in various tissues.

CSCs are defined as stem cells which have experienced mutations, causing uncontrollable self-renewal or differentiation.

Regulated cell division abilities are lost as the cell gives rise to tumors and mutated progenitor cells, which may, in turn, also cause cancer through tumor formation.

While CSCs may seem to have little use for scientists at initial glance, many  researchers have identified that CSCs are ideal for different types of targeted stem cell therapies.

If scientists can identify CSCs for a particular cancer, they can be stopped with either intensive chemotherapy, irradiation, or novel drug delivery through the use of vectors, such as disabled viruses and extremely small nanoparticles.

University of York researchers revealed that prostate cancer stem cells, for example, have unique gene expression signatures which can be used to identify them. Pancreatic cancer stem cells were also recently identified by researchers at the University of Michigan. MIT researchers recently created breast cancer stem cells in a Petri dish.

Cancer treatments developed for CSCs can be much more far-lasting than traditional treatments which target tumors. This is because of the fact that treatments developed for CSCs seek to cure the root of cancer, rather than one of the "products" of CSCs (tumors).

Biomedical researchers are currently working on altering CSCs with novel therapeutics to destroy any oncological potential they may have.

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See the video on the right made by the Ontario Science Center to review your knowledge of some key stem cell basics.  

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This visual from the NIH "Stem Cell Information" website shows some of the scientific challenges researchers face in human stem cell research. (Image Citation 62)

In the past years, while scientists have understood much about how stem cells work in the human body, a few scientific challenges remain that have yet to be solved.

For example, it is not entirely known how exactly the cell cycle and differentiation is controlled in stem cells. What prevents them from dividing for longer-than normal periods of time and causing cancer? What factors coax stem cells into differentiating into a particular type of cell in a particular region of the human body?

According to a ScienceDaily article, although iPSCs present a novel replacement for hESCs for use in research, scientists do not know whether the developmental potential in iPSCs is equivalent to that of hESCs.

Finally, innovation in the entire stem cell field is still ongoing, with new career programs and infrastructure designed to support stem cell scientists.

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