STEM CELL THERAPY

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.