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BIOTECHOLOGY
Stem Cell Differentiation
STEM CELLS
FACT SHEET
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Stem Cell Differentiation
What is Stem Cell Differentiation?
Generation of Specialized Cells from Stem Cells
Scientists and doctors are excited about the potential of stem cells to revolutionize medicine. The
promise of stem cells lies in their ability to change from an unspecialized cell into a specialized cell such
as a nerve, muscle or bone cell. Currently, doctors do not have access to a renewable source of tissue
that can be used in transplantations to restore damaged or destroyed tissue. Stem cells could be used
as a tissue source for transplantation therapy. For example, insulin-secreting pancreas cells created
from stem cells have the potential to treat Diabetes. These stem cell-derived pancreas cells could
replace dysfunctional cells in the pancreas, allowing a patient to regulate their blood sugar levels.
Another use of stem cells is to make specific cell types for studying human disease in the laboratory. For
example, in Parkinson’s disease, neurons of the brain die resulting in motor and brain defects. But the
reason why these neurons die is unknown. Scientists cannot easily access neurons from Parkinson’s
patients, so they are trying to make neurons directly from stem cells, in the laboratory. Scientists are
now using these neurons made from the stem cells of Parkinson’s patients to research the causes of this
disease.
In order to use stem cells to treat disease or as research tools to study disease, scientists must be able
to differentiate stem cells into fully functioning specialized cells. Differentiation is the process where an
unspecialized cell acquires cellular traits that allow it to perform specialized functions. Scientists are
currently working on methods to effectively differentiate stem cells into functional specialized cells.
How do stem cells differentiate during embryonic development?
The best approach to stem cell differentiation is to apply what developmental biologists have learned
about embryonic development. During development, cells of the embryo make a number of cell fate
decisions that result in decreasing potency eventually producing specialized cells (see Stem Cells and
Types of Stem Cells). Cells of the embryo make cell fate decisions based on a number of chemical and
physical signals that are produced within the embryo including; secreted chemicals from neighbouring
cells, direct communication with neighbouring cells by cell-cell contact or mechanical strain caused by
movements of the embryo as it develops. All of these processes activate signaling that ultimately leads
to changes in gene activity, which determines cellular differentiation. Stem cell biologists try to push
stem cells to differentiate into specialized cell types by recreating an embryonic environment in a petri
dish.
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BIOTECHOLOGY
Stem Cell Differentiation
STEM CELLS
FACT SHEET
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How do scientists differentiate stem cells in a dish?
To recreate embryonic development in a dish, stem cells are exposed to chemical or physical signals
that will cause cellular differentiation including:
• Growth Factors Signalling molecules that cause cellular differentiation can be added to
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stem cell culture medium to transform stem cells into specialized cell types.
Cell Culture Substrate: Stem cells can be cultured on top of extracellular matrix proteins
(proteins secreted by cells into the extracellular space) to cause differentiation.
Co-culture Environments: Cells produce signalling molecules that neighbouring cells
can respond to. Stem cells can be grown together with other cells that produce growth
factors that will cause differentiation.
Three-dimensional Culture: Stem cells can be cultured in three-dimensional aggregates
(spherical clumps of cells) called embryoid bodies to create mechanical stimulation and
cell contact. Embryoid bodies recreate an early developmental process called
gastrulation, a process that establishes the three primary germ layers.
Signal Inhibition: In addition to providing activating signals to cause cellular
differentiation, signals that cause the differentiation of stem cells to cell types other than
the cell type of interest can be inhibited. This can be accomplished by using inhibitory
growth factors.
The production of pancreas cells from pluripotent stem cells is an example of stem cell differentiation
using a number of the tools described above. To create pancreas cells, stem cells are grown as
embryoid bodies in combination with a number of pancreas-inducing growth factors. After a few days of
three-dimensional culture, the cells are separated into single cells and then grown in a two-dimensional
environment with another set of growth factors that will drive differentiation to mature pancreas cells.
How do scientists determine if stem cells have differentiated into a
specialized cell type?
Scientific Proof of Differentiated Cells
Before a scientist can claim that a stem cell has differentiated into a specialized cell, a number of criteria
must be met to prove that a stem cell has turned into a functional specialized cell:
• Appearance: Does the differentiated cell LOOK like the target cell type?
The unique combination of genes that are on and off determines the characteristics of a
unique cell type. Scientists can use a number of laboratory techniques to determine
which genes are turned on or off in a cell. For example, does the neuron that has been
created from a stem cell have the same sets of gene turned on and off as a neuron from
the brain? Cells are also unique in shape depending on the function they perform within
the body. Neurons have long, thin projections that are used to transmit signals
throughout the body. Scientists use imaging techniques to determine whether a neuron
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Copyright Let’s Talk Science © 2013
Developed in collaboration with Stem Cell Network
BIOTECHOLOGY
Stem Cell Differentiation
STEM CELLS
FACT SHEET
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made from a stem cell has the same type of long, thin projections as a neuron from the
brain.
• Behaviour: Does the differentiated cell BEHAVE like the target cell type?
Specialized cells perform specialized functions within the body. For example, heart
muscle cells contract and relax to pump blood throughout the body. In the laboratory, a
number of experiments can be performed to test whether a differentiated cell can perform
the function of a specialized cell. Scientists can see heart cells created from stem cells
beating (contacting and relaxing) in the dish using a microscope (in fact, you can see
heart cells beating on YouTube). In the body, heart muscle cells respond to electrical
signals for the cue to contract. In the laboratory, the ability of heart cells to respond to
electrical signals can be tested.
• Safety: Are the differentiated cells SAFE for use in transplantation therapy?
If specialized cells generated from stem cells are to be used to treat human disease, they
must be fully differentiated, that is, they must have lost their ability to generate any other
cell type. When undifferentiated stem cells are transplanted into a mouse, the cells will
form a tumour known as a teratoma. Teratomas are a mass made up of various cell
types. Following differentiation of stem cells, scientists must be sure that the stem cells
have lost their ability to form teratomas before they are transplanted into patients.
www.explorecuriocity.org
Copyright Let’s Talk Science © 2013
Developed in collaboration with Stem Cell Network