Download What is a Stem Cell?

What is a Stem Cell?
By Crystal Ruff, PhD
and Michael Fehlings, MD, PhD, FRCSC, FACS
Many of us have heard of the term “stem cells” in the context of various diseases, but how many of us really know what these
are and what they can and cannot do? This article explores the most common types of stem cells and describes what they are,
what they become and what resources are available for people wanting to learn more about them.
Totipotent Cell
<4 day blastocyst
Toti - “All”, Potens - “Powerful”
After the egg and sperm fuse, totipotent cells are found with the first few cell divisions of the early
blastocyst and can produce all the different cells of an organism, including tissues like placenta and
umbilical cord that aren’t part of the embryo.
Totipotent cells have total potential or total plasticity, but are rarely used for therapeutic purposes
because they are so unspecialized - you would not want them turning into bone tissue inside your
brain, for example.
... After about 4 days of cell division, totipotent cells differentiate (develop) into pluripotent cells.
Plurimus - “Many”, Potens - “Powerful”
Embryonic (derived from the embryo) Pluripotent cells are most
commonly associated with the term, “stem cells.”
On the fourth day of development, the embryo forms into two layers,
an an outer layer which will become the placenta (blue), and an inner
>4 day blastocyst
Pluripotent Cell
Blue -> Placenta
ex. ESC (above)
layer which will form the tissues of the body (green). The inner (green)
Green ->
or iPSC (below)
pluripotent cells can form any tissue in the human body, but not the
Developing
Can become any cell in body
placenta or umbilical tissue (blue).
Animal
Pluripotent cells should never be used for transplants due to their
potential to become or “differentiate into” unwanted tissue types.
SPECIAL CASE: Induced Pluripotent Stem Cells - iPSCs
In addition to stem cells that have been derived from an embryo, pluripotent cells can now be made from a patient’s
own adult cells (termed “induced pluripotent stem cells” or iPSCs)
These were discovered in 2006 so experimentation is still in early stages.
iPSCs do not use embryonic tissue; instead they use patient skin or blood.
Since they are from one’s own tissue, they are patient-specific – potentially eliminating the need for donor waiting lists.
iPSCs are not yet ready for human testing, as the most common way to get them involves use of viruses and other
factors which are not safe for humans. Scientists also do not know if there are other long-term negative side effects.
The Different Types
of Stem Cells
MSCs
Neuron
Cells of other Types
Astrocyte
Totipotent Cell
<4 day blastocyst
>4 day blastocyst
Pluripotent Cell
Blue -> Placenta
ex. ESC (above)
Green ->
or iPSC (below)
Developing
Can become any cell in body
Animal
Oligodendrocyte
Multipotent Cell
Fate-Restricted Precursors Differentiated Cells
ex. NPCs
ex. OPCs
Ex. Neuron,
Can become several,
Early cell that will only
Astrocyte,
but not all, cell types become a certain cell type
Oligodendrocyte
Virus
Small Molecule
Plasmid
Protein
RNA
Adult Differentiated Cell
(usually a skin fibroblast)
iPSCs go backward before they go forward
Differentiated/Less Pluripotent
De-Differentiated/More Pluripotent
For pluripotent cells to be used in successful stem cell therapy, they must be “differentiated” into more mature cells
that can only become one or two cell types.
... As pluripotent stem cells continue to divide, they begin to specialize into multipotent cells.
MSCs
Neuron
Cells of other Types
Astrocyte
Oligodendrocyte
Multipotent Cell Fate-Restricted Precursors Differentiated Cells
ex. NPC
ex. OPCs
Ex. Neuron,
Can become several,
Early cell that will only
Astrocyte,
but not all, cell types become a certain cell type
Oligodendrocyte
Multus - “Many”, Potens - “Powerful”
Multipotent cells are more specialized cells that can be made from
pluripotent cells in the lab or that descend from pluripotent cells
during development.
Multipotent cells produce different cell types, but only within a
specific type of tissue.
For example, Mesenchymal Stem Cells (here, MSCs) become blood,
bone, muscle and fat; neural stem (and precursor/progenitor) cells
(here, NPCs) eventually become different types of brain tissue, called
neurons, astrocytes and oligodendrocytes.
Fate-Restricted Precursors can only become one cell type.
More restricted fate-restricted precursors, such as oligodendrocyte
precursor cells (here, OPCs) can only become one mature cell type
such as an insulating oligodendrocyte.
Practically, these are the cells that are most often transplanted into a damaged tissue to promote repair.
It is IMPORTANT to note, however, that all multipotent cells are not equal – MSCs DO NOT turn into brain or spinal
cord tissue when transplanted into the body– only bone/blood/muscle/fat. Likewise, NPCs only turn into brain,
not blood, bone or muscle.
Stem cell type is an important consideration.
MSC intravenous injection has been used safely for years in leukaemia, but there is little and conflicting evidence
that it works for other uses, especially brain or spinal cord repair.
NPC neural stem cell transplant is more promising (and fate-restricted OPC transplant is most promising) for brain and
spinal cord repair in the lab, as these cells can actually become the type of insulating cells that are missing; however
clinical trials are just beginning and we do not yet know if they are safe.
Important things to Remember:
1) ALL stem cell therapy for neural repair is experimental. You will NEVER be asked to pay for an experimental
treatment from a legitimate organization. Legitimate clinical trials are required to register with the website
clinicaltrials.gov. So, if you are looking for more information on real treatments and clinical trials, or would like to
become involved, look there first.
2) Stem cell treatment could lead to neuropathic PAIN, as well as a worsened condition.
3) Going to an unregulated clinic abroad will exclude you from future legitimate clinical trials.
4) Perhaps most importantly...
Once stem cells are put in, they cannot be taken back out!
So do your homework, be knowledgeable and be safe!
Stem Cell Facts: Where to Look
NeuroDevNet - Canada’s Leading Consortium on Neurodevelopmental disorders, with several documents on stem cell therapy.
http://www.neurodevnet.ca/kt/stem-cells
Global 16x9 “Selling Hope” - An excellent investigative news report on the realities of the “stem cell therapy” business.
http://www.globalnews.ca/Pages/Story.aspx?id=6442554591
Clinicaltrials.gov - Website providing current information on ALL legitimate, registered clinical trials.
clinicaltrials.gov.
International Society for Stem Cell Research (ISSCR) - A world leader for stem cell research with a wealth of educational material.
http://www.isscr.org/public
http://www.closerlookatstemcells.org/
Canadian Institutes of Health Research - CIHR Stem Cell Research page provides up-to-date information on stem cell governance & legislature.
http://www.cihr-irsc.gc.ca/e/15255.html
National Institutes of Health Research - A government-sponsored initiative providing up-to-date information on stem cells in regenerative medicine.
http://stemcells.nih.gov/