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Posted by
Dr. Frank Yap, MD
Stem Cell Basics: What You Need to Know (2024)
Stem cell therapy has gained popularity globally as a promising alternative treatment option for anti-aging, cosmetic and also conditions where the current medical treatment protocols have been exhausted. However, there is also a lot of confusion due to the overwhelming mixing of credible scientific information and marketing hypes available on the internet.
We have compiled a comprehensive guide about stem cells below in layman's terms so that you can understand and hopefully make a better informed decision.
Stem Cell Basics
This guide on stem cells is intended for anyone who wishes to learn more about
stem cells, the important questions about stem cells that are the focus of
scientific research, and the potential use of stem cells in research and in
treating disease. This includes information about stem cells derived from
embryonic and non-embryonic tissues. Much of the information included here is
about stem cells derived from human tissues, but some studies of animal-derived
stem cells are also described.
Contents:
Introduction: What are stem cells, and why are they important?
What are the unique properties of all stem cells?
What are embryonic stem cells?
What are adult stem cells?
What are induced pluripotent stem cells?
What are the potential uses of human stem cells?
Where can I get more information?
Introduction: What are stem cells, and why are they important?
Stem cells have the remarkable potential to develop into many different cell
types in the body during early life and growth. In addition, in many tissues
they serve as a sort of internal repair system, dividing essentially without
limit to replenish other cells as long as the person or animal is still alive.
When a stem cell divides, each new cell has the potential either to remain a
stem cell or become another type of cell with a more specialized function,
such as a muscle cell, a red blood cell, or a brain cell.
Stem cells are distinguished from other cell types by two important
characteristics. First, they are unspecialized cells capable of renewing
themselves through cell division, sometimes after long periods of
inactivity. Second, under certain physiologic or experimental conditions,
they can be induced to become tissue- or organ-specific cells with special
functions. In some organs, such as the gut and bone marrow, stem cells
regularly divide to repair and replace worn out or damaged tissues. In other
organs, however, such as the pancreas and the heart, stem cells only divide
under special conditions.
Until recently, scientists primarily worked with two types of stem cells
from animals and humans: embryonic stem cells and non-embryonic "somatic" or
"adult" stem cells. The functions and characteristics of these cells will be
explained in this document. Scientists discovered ways to derive embryonic
stem cells from early mouse embryos more than 30 years ago, in 1981. The
detailed study of the biology of mouse stem cells led to the discovery, in
1998, of a method to derive stem cells from human embryos and grow the cells
in the laboratory. These cells are called human embryonic stem cells. The
embryos used in these studies were created for reproductive purposes through
in vitro fertilization procedures. When they were no longer needed for that
purpose, they were donated for research with the informed consent of the
donor. In 2006, researchers made another breakthrough by identifying
conditions that would allow some specialized adult cells to be
"reprogrammed" genetically to assume a stem cell-like state. This new type
of stem cell, called induced pluripotent stem cells (iPSCs), will be
discussed in a later section of this document.
Stem cells are important for living organisms for many reasons. In the 3- to
5-day-old embryo, called a 'blastocyst', the inner cells give rise to the
entire body of the organism, including all of the many specialized cell
types and organs such as the heart, lungs, skin, sperm, eggs and other
tissues. In some adult tissues, such as bone marrow, muscle, and brain,
discrete populations of adult stem cells generate replacements for cells
that are lost through normal wear and tear, injury, or disease.
Given their unique regenerative abilities, stem cells offer new potentials
for treating diseases such as diabetes, and heart disease. However, much
work remains to be done in the laboratory and the clinic to understand how
to use these cells for cell-based therapies to treat disease, which is also
referred to as regenerative or reparative medicine.
Laboratory studies of stem cells enable scientists to learn about the
cells’ essential properties and what makes them different from specialized
cell types. Scientists are already using stem cells in the laboratory to
screen new drugs and to develop model systems to study normal growth and
identify the causes of birth defects.
Research on stem cells
continues to advance knowledge about how an organism develops from a
single cell and how healthy cells replace damaged cells in adult
organisms. Stem cell research is one of the most fascinating areas of
contemporary biology, but, as with many expanding fields of scientific
inquiry, research on stem cells raises scientific questions as rapidly as
it generates new discoveries.
What are the unique properties of all stem cells?
Stem cells differ from other kinds of cells in the body. All stem cells—regardless of their source—have three general properties: they are capable of dividing and renewing themselves for long periods; they are unspecialized; and they can give rise to specialized cell types.
Stem cells are capable of dividing and renewing themselves for long periods. Unlike muscle cells, blood cells, or nerve cells—which do not normally replicate themselves—stem cells may replicate many times, or proliferate. A starting population of stem cells that proliferates for many months in the laboratory can yield millions of cells. If the resulting cells continue to be unspecialized, like the parent stem cells, the cells are said to be capable of long-term self-renewal.
Scientists are trying to understand two fundamental properties of stem
cells that relate to their long-term self-renewal:
Why can embryonic stem cells proliferate for a year or more in
the laboratory without differentiating, but most adult stem
cells cannot; and
What are the factors in living organisms that normally regulate stem
cell proliferation and self-renewal?
Discovering the answers to these questions may make it possible to
understand how cell proliferation is regulated during normal embryonic
development or during the abnormal cell division that leads to
cancer. Such information would also enable scientists to grow embryonic
and non-embryonic stem cells more efficiently in the laboratory.
The specific factors and conditions that allow stem cells to remain
unspecialized are of great interest to scientists. It has taken scientists
many years of trial and error to learn to derive and maintain stem cells
in the laboratory without them spontaneously differentiating into specific
cell types. For example, it took two decades to learn how to
grow human embryonic stem cells in the laboratory following the
development of conditions for growing mouse stem cells. Likewise,
scientists must first understand the signals that enable a
non-embryonic (adult) stem cell population to proliferate and remain
unspecialized before they will be able to grow large numbers of
unspecialized adult stem cells in the laboratory.
Stem cells are unspecialized. One of the fundamental properties of a stem cell is that it does
not have any tissue-specific structures that allow it to perform
specialized functions. For example, a stem cell cannot work with its
neighbors to pump blood through the body (like a heart muscle cell), and
it cannot carry oxygen molecules through the bloodstream (like a red blood
cell). However, unspecialized stem cells can give rise to specialized
cells, including heart muscle cells, blood cells, or nerve cells.
Stem cells can give rise to specialized cells. When unspecialized stem cells give rise to specialized cells, the
process is called differentiation. While differentiating, the cell
usually goes through several stages, becoming more specialized at each
step. Scientists are just beginning to understand the signals inside and
outside cells that trigger each step of the differentiation process. The
internal signals are controlled by a cell's genes, which
are interspersed across long strands of DNA and carry coded instructions
for all cellular structures and functions. The external signals for cell
differentiation include chemicals secreted by other cells, physical
contact with neighboring cells, and certain molecules in
the microenvironment. The interaction of signals during
differentiation causes the cell's DNA to
acquire epigenetic marks that restrict DNA expression in the
cell and can be passed on through cell division.
Many questions about stem cell differentiation remain. For example, are
the internal and external signals for cell differentiation similar for all
kinds of stem cells? Can specific sets of signals be identified that
promote differentiation into specific cell types? Addressing these
questions may lead scientists to find new ways to control stem cell
differentiation in the laboratory, thereby growing cells or tissues that
can be used for specific purposes such as cell-based
therapies or drug screening.
Adult stem cells typically generate the cell types of the tissue in which
they reside. For example, a blood-forming adult stem cell in the bone
marrow normally gives rise to the many types of blood cells. It is
generally accepted that a blood-forming cell in the bone marrow—which is
called a hematopoietic stem cell—cannot give rise to the cells of a
very different tissue, such as nerve cells in the brain. Experiments over
the last several years have purported to show that stem cells from one
tissue may give rise to cell types of a completely different tissue. This
remains an area of great debate within the research community. This
controversy demonstrates the challenges of studying adult stem cells and
suggests that additional research using adult stem cells is necessary to
understand their full potential as future therapies.
Where do stem cells come from?
Stem cells can be obtained from a variety of sources including; umbilical cord tissue, umbilical cord blood, bone marrow, adipose (fat) tissue, placental tissue, dental pulp, and embryos. There are two main types of stem cells: embryonic stem cells, which come from embryos, and adult stem cells, which come from fully developed tissues such as the brain, skin, umbilical cord tissue and bone marrow. A third type of human engineered stem cell (Induced pluripotent stem cells) are adult stem cells that have been changed in a lab to be more like embryonic stem cells. There are several different types of stem cells, including:
Embryonic stem cells (ESCs)
Adult stem cells (ASCs)
Induced pluripotent stem cells (iPSCs)
What are embryonic stem cells?
What stages of early embryonic development are important for
generating embryonic stem cells?
Embryonic stem cells, as their name suggests, are derived from embryos. Most
embryonic stem cells are derived from embryos that develop from eggs that
have been fertilized in vitro—in an in vitro fertilization (IVF) clinic—and
then donated for research purposes with informed consent of the donors. They
are not derived from eggs fertilized in a woman's body.
How are embryonic stem cells grown in the laboratory?
Growing cells in the laboratory is known as cell culture. Human
embryonic stem cells (hESCs) are generated by transferring cells from a
preimplantation-stage embryo into a plastic laboratory culture dish that
contains a nutrient broth known as culture medium. The cells divide and
spread over the surface of the dish. In the original protocol, the inner
surface of the culture dish was coated with mouse embryonic skin cells
specially treated so they will not divide. This coating layer of cells is
called a feeder layer. The mouse cells in the bottom of the culture dish
provide the cells a sticky surface to which they can attach. Also, the
feeder cells release nutrients into the culture medium. Researchers have now
devised ways to grow embryonic stem cells without mouse feeder cells. This
is a significant scientific advance because of the risk that viruses or
other macromolecules in the mouse cells may be transmitted to the human
cells.
How are embryonic stem cells stimulated to differentiate?
As long as the embryonic stem cells in culture are grown under appropriate
conditions, they can remain undifferentiated (unspecialized). But if cells
are allowed to clump together to form embryoid bodies, they begin to
differentiate spontaneously. They can form muscle cells, nerve cells, and
many other cell types. Although spontaneous differentiation is a good
indication that a culture of embryonic stem cells is healthy, the process is
uncontrolled and therefore an inefficient strategy to produce cultures of
specific cell types.
So, to generate cultures of specific types of differentiated cells—heart
muscle cells, blood cells, or nerve cells, for example—scientists try to
control the differentiation of embryonic stem cells. They change the
chemical composition of the culture medium, alter the surface of the culture
dish, or modify the cells by inserting specific genes.
If scientists can reliably direct the differentiation of embryonic stem
cells into specific cell types, they may be able to use the resulting,
differentiated cells to treat certain diseases in the future. Diseases that
might be treated by transplanting cells generated from human embryonic stem
cells include diabetes, traumatic spinal cord injury, Duchenne's muscular
dystrophy, heart disease, and vision and hearing loss.
What are adult stem cells?
An adult stem cell is thought to be an undifferentiated cell, found among
differentiated cells in a tissue or organ. The adult stem cell can renew
itself and can differentiate to yield some or all of the major specialized
cell types of the tissue or organ. The primary roles of adult stem cells in a
living organism are to maintain and repair the tissue in which they are found.
Scientists also use the term somatic stem cell instead of adult stem cell,
where somatic refers to cells of the body (not the germ cells, sperm or eggs).
Unlike embryonic stem cells, which are defined by their origin (cells from the
preimplantation-stage embryo), the origin of adult stem cells in some mature
tissues is still under investigation.
Research on adult stem cells has generated a great deal of excitement.
Scientists have found adult stem cells in many more tissues than they once
thought possible. This finding has led researchers and clinicians to ask
whether adult stem cells could be used for transplants. In fact, adult
hematopoietic, or blood-forming, stem cells from bone marrow have been used in
transplants for more than 40 years. Scientists now have evidence that stem
cells exist in the brain and the heart, two locations where adult stem cells
were not at first expected to reside. If the differentiation of adult stem
cells can be controlled in the laboratory, these cells may become the basis of
transplantation-based therapies.
Where are adult stem cells found, and what do they normally do?
Adult stem cells have been identified in many organs and tissues, including
brain, bone marrow, peripheral blood, blood vessels, skeletal muscle, skin,
teeth, heart, gut, liver, ovarian epithelium, and testis. They are thought to
reside in a specific area of each tissue (called a "stem cell niche"). In many
tissues, current evidence suggests that some types of stem cells are
pericytes, cells that compose the outermost layer of small blood vessels. Stem
cells may remain quiescent (non-dividing) for long periods of time until they
are activated by a normal need for more cells to maintain tissues, or by
disease or tissue injury.
Typically, there is a very small number of stem cells in each tissue and, once
removed from the body, their capacity to divide is limited, making generation
of large quantities of stem cells difficult. Scientists in many laboratories
are trying to find better ways to grow large quantities of adult stem cells in
cell culture and to manipulate them to generate specific cell types so they
can be used to treat injury or disease. Some examples of potential treatments
include regenerating bone using cells derived from bone marrow stroma,
developing insulin-producing cells for type 1 diabetes, and repairing damaged
heart muscle following a heart attack with cardiac muscle cells.
What tests are used to identify adult stem cells?
Scientists often use one or more of the following methods to identify adult
stem cells: (1) label the cells in a living tissue with molecular markers and
then determine the specialized cell types they generate; (2) remove the cells
from a living animal, label them in cell culture, and transplant them back
into another animal to determine whether the cells replace (or "repopulate")
their tissue of origin.
Importantly, scientists must demonstrate that a single adult stem cell can
generate a line of genetically identical cells that then gives rise to all the
appropriate differentiated cell types of the tissue. To confirm experimentally
that a putative adult stem cell is indeed a stem cell, scientists tend to show
either that the cell can give rise to these genetically identical cells in
culture, and/or that a purified population of these candidate stem cells can
repopulate or reform the tissue after transplant into an animal.
What is known about adult stem cell differentiation?
As indicated above, scientists have reported that adult stem cells occur in
many tissues and that they enter normal differentiation pathways
to form the specialized cell types of the tissue in which they reside.
Normal differentiation pathways of adult stem cells. In a living animal, adult stem cells are available to divide for a
long period, when needed, and can give rise to mature cell types that have
characteristic shapes and specialized structures and functions of a
particular tissue.
Hematopoietic stem cells give rise to all the types of blood cells: red
blood cells, B lymphocytes, T lymphocytes, natural killer cells,
neutrophils, basophils, eosinophils, monocytes, and macrophages.
Mesenchymal stem cells have been reported to be present in many tissues.
Those from bone marrow (bone marrow stromal stem cells, skeletal stem
cells) give rise to a variety of cell types: bone cells (osteoblasts and
osteocytes), cartilage cells (chondrocytes), fat cells (adipocytes), and
stromal cells that support blood formation. However, it is not yet clear
how similar or dissimilar mesenchymal cells derived from non-bone marrow
sources are to those from bone marrow stroma.
Neural stem cells in the brain give rise to its three major cell types:
nerve cells (neurons) and two categories of non-neuronal cells—astrocytes
and oligodendrocytes.
Epithelial stem cells in the lining of the digestive tract occur in deep
crypts and give rise to several cell types: absorptive cells, goblet
cells, Paneth cells, and enteroendocrine cells.
Skin stem cells occur in the basal layer of the epidermis and at the base
of hair follicles. The epidermal stem cells give rise to keratinocytes,
which migrate to the surface of the skin and form a protective layer. The
follicular stem cells can give rise to both the hair follicle and to the
epidermis.
Transdifferentiation. A number of experiments have reported that
certain adult stem cell types can differentiate into cell types seen in organs
or tissues other than those expected from the cells' predicted lineage (i.e.,
brain stem cells that differentiate into blood cells or blood-forming cells
that differentiate into cardiac muscle cells, and so forth). This reported
phenomenon is called transdifferentiation.
In addition to reprogramming cells to become a specific cell type, it is now
possible to reprogram adult somatic cells to become like embryonic stem cells
(induced pluripotent stem cells, iPSCs) through the introduction of embryonic
genes. Thus, a source of cells can be generated that are specific to the
donor, thereby increasing the chance of compatibility if such cells were to be
used for tissue regeneration. However, like embryonic stem cells,
determination of the methods by which iPSCs can be completely and reproducibly
committed to appropriate cell lineages is still under investigation.
What are mesenchymal stem cells (MSCs)?
MSCs are adult stem cells that have self-renewal, immunomodulatory, anti-inflammatory, signaling, cell division, and differentiation properties. MSCs self-renewal capacity is characterized by their ability to divide and develop into multiple specialized cell types in a specific tissue or organ. MSCs may become unique stem cell types and create more stem cells when placed in cell culture and undergo Vitro fertilization. (Vitro fertilization can help grow stem cells in a laboratory setting. MSCs can also replace cells that are damaged or diseased. MSCs can be sourced from a variety of tissue, including adipose tissue (fat), bone marrow, umbilical cord tissue, blood, liver, dental pulp, and skin.
Clinical trials and MSCs
MSCs are widely used in treating various diseases due to their self-renewable, differentiation, anti-inflammatory, and immunomodulatory properties. In-vitro (performed in a laboratory setting) and in-vivo (taking place in a living organism) studies have supported an understanding of the mechanisms, safety, and efficacy of MSC therapy in clinical applications.
Where do mesenchymal stem cells come from?
Mesenchymal Stem cells can be obtained from many different sources. Stem cell research indicates that these include adipose (fat tissue), umbilical cord tissue, placental tissue, umbilical cord blood, or bone marrow.
Mesenchymal stem cells are adult stem cells that have self-renewal, immunomodulatory, anti-inflammatory, signaling, and differentiation properties. Mesenchymal stem cells (MSCs) self-renewal capacity is characterized by their ability to divide and develop into multiple specialized cell types in a specific tissue or organ. MSCs can become neural stem cells
MSCs can differentiate into tissue-specific stem cells, including cells of the bone, cartilage, heart muscle cells, brain cells, and adipose tissue. While MSCs are not typically thought of as neural cells, some studies have shown that MSCs can differentiate into cells with neural characteristics under certain conditions.
One study found that MSCs treated with specific growth factors and exposed to a neural induction medium could differentiate into cells with characteristics of both neurons and glial cells, which are types of cells that support and protect neurons in the nervous system.
However, the degree to which MSCs can differentiate into fully functional neural cells remains uncertain. More research is needed to fully understand the potential of MSCs to differentiate into neural cells and the potential use of MSCs in treating neural disorders.
UC-MSCs can be sourced from a variety of areas including Wharton’s Jelly, cord lining, and peri-vascular region of the umbilical cord. As a commonly discarded tissue, the umbilical cord contains a rich source of mesenchymal stromal cells, which are therefore obtained non-invasively.
UC-MSCs are the most primitive type of MSCs, shown by their higher expression of Oct4, Nanog, Sox2, and KLF4 markers.
Umbilical cord tissue-derived mesenchymal stem cells have the ability to differentiate into different cell types and have the greatest proliferation rate of the three mentioned types of stem cells (adipose, bone marrow, cord tissue).
Similar to adipose tissue and bone marrow-derived MSCs, UC-MSCs are known to secrete growth factors, cytokines, and chemokines, improving different cell repair mechanisms. These functions all assist the anti-inflammatory and immunomodulatory properties of MSCs.
Pictured: Umbilical cord tissue diagram showing where stem cells originate
Why use umbilical cord tissue?
Cord tissue is rich in mesenchymal stem cells, potentially used to help heal, regenerate & treat a variety of conditions. Mesenchymal Stem Cells (MSCs) derived from umbilical cord tissue have shown the ability to avoid a negative response from a person’s immune system, allowing the cells to be transplanted in a wide range of people without fear of rejection. These transplants may have the ability to vastly increase the body’s natural healing abilities and have robust anti-inflammatory and immunosuppressive responses.
What are induced pluripotent stem cells?
Induced pluripotent stem cells (iPSCs) are adult cells that have been
genetically reprogrammed to an embryonic stem cell–like state by being forced
to express genes and factors important for maintaining the defining properties
of embryonic stem cells. Although these cells meet the defining criteria for
pluripotent stem cells, it is not known if iPSCs and embryonic stem cells
differ in clinically significant ways. Mouse iPSCs were first reported in
2006, and human iPSCs were first reported in late 2007. Mouse iPSCs
demonstrate important characteristics of pluripotent stem cells, including
expressing stem cell markers, forming tumors containing cells from all three
germ layers, and being able to contribute to many different tissues when
injected into mouse embryos at a very early stage in development. Human iPSCs
also express stem cell markers and are capable of generating cells
characteristic of all three germ layers.
Although additional research is needed, iPSCs are already useful tools for
drug development and modeling of diseases, and scientists hope to use them in
transplantation medicine. Viruses are currently used to introduce the
reprogramming factors into adult cells, and this process must be carefully
controlled and tested before the technique can lead to useful treatment for
humans. In animal studies, the virus used to introduce the stem cell factors
sometimes causes cancers. Researchers are currently investigating non-viral
delivery strategies. In any case, this breakthrough discovery has created a
powerful new way to "de-differentiate" cells whose developmental fates had
been previously assumed to be determined. In addition, tissues derived from
iPSCs will be a nearly identical match to the cell donor and thus probably
avoid rejection by the immune system. The iPSC strategy creates pluripotent
stem cells that, together with studies of other types of pluripotent stem
cells, will help researchers learn how to reprogram cells to repair damaged
tissues in the human body.
What are the potential uses of human stem cells?
Stem cell therapy, a rapidly evolving field within regenerative medicine, has shown promising results in treating various diseases and medical conditions. Various types of stem cells, including hematopoietic stem cells, mesenchymal stem cells, and induced pluripotent stem cells, have been utilized in clinical trials and treatments. The following list of diseases treated with stem cells is based on peer-reviewed data from sources such as the National Library of Medicine (www.ncbi.nlm.nih.gov), which provide an overview of diseases and conditions that have been treated with stem cell therapies:
http://www.explorestemcells.co.uk
A United Kingdom-based resource for the general public that discusses the use
of stem cells in medical treatments and therapies.
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