What
Are Mesenchymal Stem Cells?
Mesenchymal
Stem Cells are a unique type of connective tissue that is only
partially developed and still has the ability to further specialize
into specific forms of connective tissue. The scientific term for
cells that have the ability to further evolve into different cell
types is Multipotent. You will often find this particular form of
Multipotent cell referred to as an MSC. MSCs are also referred to as
Marrow Stromal Cells when scientifically appropriate.
These
cells have the ability to develop into a number of different types of
cells, including fat cells, cartilage cells, and bone cells. As you
can imagine, there is a growing amount of interest in cultivating
Mesenchymal Stem Cells for use in a number of different medical
treatments, especially those related to bone and joint injuries. The
ability for MSCs to develop into more complex tissues has been
scientifically proven both in a laboratory environment and in animal
subjects.
Why
Are They Called Mesenchymal Stem Cells?
As
researchers learn more about these cells, coming up with an optimally
appropriate name became increasingly important:
Mesenchyme
is a preliminary form of connective tissue which evolves in the
embryo stage of development, but this name does not fully meet the
needs of MSCs. This tissue forms in the central layer of the embryo,
known as the mesoderm.
Further in
development, Mesenchyme evolves into both connective and
hematopoietic tissue, whereas Mesenchymal Stem Cells can only develop
into connective tissue, which proves that Mesenchyme and MSCs are
related cells, but different..
Stromal
Cell refers to a different aspect of MSC function. These cells
are a form of connective tissue that provides structural support to
a larger cell. Stromal Cell is accurate enough of a term to describe
one way that the body uses MSCs, but does not encapsulate the full
form and function of the cell.
This is
because it has only recently been determined that MSCs have the
ability to facilitate the healing of damaged tissue, which
necessitates a broader set of naming conventions for the cellular
type.
This is
why cells that were once almost universally described as Marrow
Stromal Cells are now commonly referred to as MSCs by researchers.
Now it is clear that these MSCs exist throughout the body in a
variety of different forms of tissue including corneal stroma, adult
muscle, adipose tissue, and umbilical cord blood.
They even
exist in the core of the baby teeth. In spite of their multipotent
configuration, they do not have the ability to recreate a whole
organ, which is why the new naming convention Multipotent Stromal
Cell is becoming more common.
When
do Mesenchymal Stem Cells Develop?
The earliest form of MSCs that are manifest during prenatal
development can be found in the tissue of the umbilical cord,
specifically in the blood of the cord and in Wharton's Jelly.
Although MSCs are present in the blood of the umbilical cord, they
are present in greater concentrations in Wharton's Jelly, which is
also a significant source of stem cells which develop into blood
cells of various types, known as Hematopoietic Stem Cells.
MSCs
Found in the Umbilical Cord
Today, umbilical cords are simply discarded after a successful
pregnancy, but there is growing evidence that these umbilical cords
may be a fantastic and safe method of obtaining these primitive MSCs
for medical research and treatment.
Mesenchymal
Stem Cells Found in the Molars
Another
area that is dense in MSCs is the third childhood molar of the lower
jawbone. These cells are considered multipotent as of today, but
initial research provides evidence that these cells may actually be
pluripotent. Mesenchymal Stem
Cells develop into a variety of different tissues, including nervous
tissues, dental pulp, blood vessels, dentin, and enamel. All told,
there are at lease twenty-nine different organs produced from MSCs.
Also,
because these teeth can generally be harvested before ten years of
age, naturally, with negligible mortality risk, there is a high
probability that this source of MSCs will become a significant source
of MSCs for treatment, research, and that patients may even be
recommended to save them for future potential therapeutic use. MSCs
also have the capability to develop into liver cells.
Mesenchymal
Stem Cells Found in the Amniotic Fluid
Another concentrated source of MSCs is in the amniotic fluid of the
placenta. Evidence suggests that at least one percent of the cells in
the amniotic fluid are pluripotent MSCs
Mesenchymal
Stem Cells Found in Adipose Fat
After childhood, one of the most concentrated sources of Mesenchymal
Stem Cells is in Adipose Fat Tissue. Medical research has shown that
in a single gram of adipose fat has more than five hundred times the
MSCs as an equivalent amount of aspirated bone marrow. For this
reason, there is a lot of research going on right now with regard to
using MSCs found in fat cells for the treatment of various medical
conditions.
Mesenchymal
Stem Cells May be Found Within Peripheral Blood Cells
There is
some evidence that Mesenchymal Stem Cells may be found in sufficient
concentrations in Peripheral Blood Cells, but this evidence is far
from conclusive. A few studies have been able to extract MSCs from
these blood cells and been able to foster them in culture, however.
The
History of Mesenchymal Blood Cells
A medical
researcher named Alexander Maximow was able to single out a
particular form of precursor tissue located in the Mesenchyme which
had the ability to evolve into a variety of hematopoietic tissue.
Later in
the 1960s, two researchers, James Till and Ernest McCulloch,
discovered that marrow cells had the ability to essentially clone
themselves. In the 1970s, a research team led by A.J. Friedenstein
was able to isolate and definitively prove the ability of Stromal
Marrow Cells to develop multipotently.
Further
study of these cells uncovered that marrow cells had a high level of
plasticity and that particular environmental triggers could alter
their development into a variety of forms of tissue. For example, if
these cells were allowed to develop in the same dish as
dexamethasone, inorganic phospate, and Vitamin C, the marrow cells
would develop into osteoblasts. On the other hand, exposure to TGF-b
would induce the cells to develop into chondrocytes.
Morpology
of Mesenchymal Stem Cells
MSCs
can be physically described as a central body with a few thin and
long processes extending out. The body of the call holds a nucleus
which is round, large, and has a conspicuous nucleolus. The nucleus
is covered in fine particles known as chromatin, which make it easy
to see.
The
rest of the cell body is occupied by polyribosomes, mitochondria,
rough endoplasmic reticulum, and limited Golgi apparatus. Each of the
cells is skinny and long, are dispersed widely, and the cells are
connected by a small number of reticular fibrils.
How Are
Mesenchymal Stem Cells Detected
The
International Society for Cellular Therapy provides the most
established definition for what qualifies as an MSC. They consider
MSCs any cell which displays malleable properties under standard
conditions and is structured like a fibroblast. There are some
medical researchers that even believe that fibroblasts and MSCs are
operatively identical.
Also, MSCs
have the ability to undergo chondrogenic, adipogenic, and osteogenic
differentiation in culture. Finally, cultured Mesenchymal Cells also
have a certain set of active and inactive enzymes on their surface.
What is
the Capacity for MSCs to Differentiate?
Mesenchymal
Stem Cells have a tremendous ability to reproduce themselves while
not losing their ability to evolve, but there is no easy way to
quantify that capacity. The general method to prove multipotency is
for a cell to be able to evolve into neurons, myocytes, chondrocytes,
adipocytes, and osteoblasts with sufficient environmental cues.
Mesenchymal Stem Cells have the capacity to develop into all of these
different types of cells, but it is unclear whether it is possible to
create a functioning neuron from an MSC.
The
ability for an MSC to develop into a particular form depends upon the
individual cell as well as the manner in which the change is
produced, whether via mechanical or chemical means, for example. It
is also unclear whether differentiation occurs because of an overall
capacity to differentiate or the proclivity of certain cells to
differentiate in their own capacity.
There is
also evidence that the older a donor is when MSCs are contributed,
the slower that the cells differentiate and proliferate. There is no
definitive evidence regarding whether this is because there are
issues in donated MSCs or a lower concentration of MSCs in a culture.
Effects
of Mesenchymal Stem Cells on the Immune System
Research
has shown that in human beings, MSCs block the function of T-Cells
and dendritic cells. They also release cytokynes, which suppress
immune response in their immediate environment. These cells alter
immune function more vigorously in an area where inflammation is
prominent.
In other
situations, however, studies have shown that these effects are not
universal and can be altered by other extenuating circumstances.
Because each isolated culture of MSCs have their own unique
configuration, the cell cultures often react in different ways to the
same stimulus.
The
Culturing of Mesenchymal Stem Cells
There are
a number of methods to develop MSC cultures, but the most prominent
is taking ficoll-purified bone marrow or unadulterated bone marrow
and placing the mononuclear cells straight into flasks or culture
plates. After one to two days, MSCs will stick to the specialized
plastic, but hematopoietic cells and red blood cells will not. There
is some evidence that this technique is not a perfect method, and at
least some MSCs do not adhere in the given time frame, if at all.
How Are
Mesenchymal Stem Cells Related to Cancer?
MSC
proliferation is involved in many forms of cancer, especially those
which impact the bone marrow. Hematological Cancers most commonly
impact the function of MSCs.
What
Are the Medical Uses for Mesenchymal Stem Cells
There are
methods currently by which MSCs can be mobilized and activated if
necessary. Unfortunately, using today's medical methods, there is a
limited efficiency. For example, muscles recover quite slowly from
injury because of this limited mobilization. There is promising
research which suggests that there may be scientific methods to speed
up this healing process.
In recent
history, there have been a number of medical success stories
involving the transplantation of MSCs directly into the blood stream
in medical conditions such as sepsis, but in many of these cases,
alternative forms of treatment have been found to be more effective,
especially in the case of conditions related to peripheral tissues.
The most
effective form of MSC administration appears to be to distribute the
cells directly to the area which requires rehabilitation. When
delivered directly to the blood stream, the lungs absorb many of the
MSCs, limiting the capacity of the treatment. MSCs have been used
frequently in an orthopedic environment, but these treatments need
more rigorous and widespread use before their effectiveness can be
fully determined.
One
physician, Dr. Wakitani, has released a set of five case studies in
which he treated five defective knees by implanting MSCs and
quantified the effectiveness of the treatment.
Effectiveness
of Cryogenically Preserved MSCs
Researchers
have shown that MSCs are highly receptive to cryogenic freezing, but
slowly regain their efficacy after they've been thawed, meaning that
they should be allowed to thaw and propagate before implantation for
maximum effectiveness. Many clinical studies have failed explicitly
because MSCs were implanted directly after they were thawed. By
allowing the cells to propagate after thawing, the cells will fully
recover from being frozen, with the cells being just as useful as if
they were never frozen.
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