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Primer on Stem Cells

By Pluristem Life Systems

 

What is a Stem Cell?

Stem cells are undifferentiated “mother” cells that have the ability to develop into any kind of cell in the human body. Dedicated non-stem cells have a specific function (e.g. liver cells, skin cells, brain cells, etc.) and once dedicated cells have taken on their function, in a process called differentiation, they can't be adapted for any other function.

Stem cells, however, have not yet differentiated. Stem cells can, theoretically, multiply and differentiate an unlimited number of times and, by doing so, replenish any and all other cells. When a stem cell divides, each new cell has the potential to either remain a stem cell or differentiate into another, more dedicated type of cell with a more specialized function, such as a muscle cell, a red blood cell, a brain cell, etc.

Classes of Stem Cells:


There are three main classes of stem cells: totipotent, pluripotent, and multipotent

* Totipotent stem cells have the potential to become all other types of cells in the body. A fertilized egg is totipotent.

* Pluripotent stem cells can produce any type of cell in the body except those needed to develop a fetus. Embryonic stem cells are produced when a newly fertilized egg begins to divide and are pluripotent.

* Multipotent stem cells can produce only certain types of cells. Adult stem cells are multipotent and are found in adults, infants and children. Mesenchymal stem cells (MSCs) are also multipotent adult stem cells and are found in the placenta as well as organs that have already developed. MSCs act as a repair and maintenance cells dividing regularly to provide the body with specialized cells to take the place of those that die or are otherwise lost.


What Is a Hematopoietic Stem Cell (HSC)?

A hematopoietic stem cell (HSC) is an adult stem cell isolated from the bone marrow, umbilical cord or peripheral blood that can renew itself, differentiate to a variety of specialized blood cells such as red and white blood cells and platelets. HSCs are exclusively required for bone marrow transplantation (BMT) and are the only cells that can reconstitute the hematopoietic or blood system following BMT. HSCs are now routinely used to treat patients with cancers and other disorders of the blood and immune systems. Examples of the diseases where BMT may be of value are the following:

 

Acute Leukemias
Acute Biphenotypic Leukemia
Acute Lymphocytic Leukemia (ALL)
Acute Myelogenous Leukemia (AML)
Acute Undifferentiated Leukemia

Chronic Leukemias
Chronic Lymphocytic Leukemia (CLL)
Chronic Myelogenous Leukemia (CML)
Juvenile Chronic Myelogenous Leukemia (JCML)
Juvenile Myelomonocytic Leukemia (JMML)

Myelodysplastic Syndromes
Amyloidosis
Chronic Myelomonocytic Leukemia (CMML)
Refractory Anemia (RA)
Refractory Anemia with Excess Blasts (RAEB)
Refractory Anemia with Excess Blasts in Transformation (RAEB-T)
Refractory Anemia with Ringed Sideroblasts (RARS)

Stem Cell Disorders
Aplastic Anemia (Severe)
Congenital Cytopenia
Dyskeratosis Congenita
Fanconi Anemia
 

 

How can stem cells be used to treat disease?

Researchers are exploring two main avenues for using stem cells to treat disease

1) Stem cells as “replacement parts”: A wide range of diseases (heart disease, Parkinson’s, Alzheimer’s, diabetes, motor neuron disease, etc.) may be amenable to stem cell therapy if stem cells can be directed to the appropriate place in the body and become the appropriate cell type. For example, if stem cells could be made to migrate to an injured spinal cord and become nerve cells, it might be possible to cure paralysis.

2) Developing drug therapies: It is possible to make stem cells that are genetically identical to those of a patient with a disease such as amyotrophic lateral sclerosis. The stem cells can be made to generate the cell type that is defective in that disease (e.g. nerve cells). By studying these cells, researchers may be able to gain insight into what goes wrong at the molecular level in the disease. They can also use these cells to test drugs that might block the progression of the disease.

Umbilical cord blood (CB) transplantations:

 

A very effective source of transplantable and readily available hematopoietic stem cells (HSCs) comes from umbilical cord blood (CB). Since the collection of CB from the donor is simple and non-invasive and the extracted stem cells are highly immunologically tolerant, CB transplantations have received tremendous attention. However, due to the small volume of blood collected from umbilical cords, transplantations have been limited to infants and children weighing less than 80 lbs. Therefore the need to develop an expansion technology that will increase the effectiveness of the small volume of blood found in the umbilical cord has become imperative for CB to become a viable option for BMT for all size individuals.

 

Pluristem believes their proprietary PluriX™ 3D bioreactor provides the solution for this needed expansion technology. In preclinical studies to date, the resultant cells from the PluriX™ 3D bioreactor, termed PLX I, has significantly improved the engraftment of the HSCs found in CB by up to 500% over controls.

WHEN HI-TECH IS APPLIED TO STEM CELLS

In the laboratory, stem cells have historically been cultivated and grown in a limited two dimensional environment using a cocktail of nutrients and growth factors.

In April 2004 Pluristem revealed its proprietary PluriX™ 3D bioreactor. Unlike conventional two-dimensional (i.e., flat) culturing, the uniqueness of the PluriX™ bioreactor is its ability to create a three dimensional microenvironment that closely resembles the structure and function of the body's bone marrow.

Pluristem’s PluriX™ 3D bioreactor, consisting of a uniquely structured ‘stromal’ cell culture, provides an optimal environment to support and maintain the expansion of mesenchymal stem cells (MSCs). MSCs are non-blood multipotent adult stem cells that contribute to the regeneration of supporting tissues including bone, cartilage, fat and muscle.


Using its PluriX™ 3D bioreactor system, Pluristem has broken new ground by developing a unique process that allows the growth of MSCs in an artificial physiological structure which closely replicates the natural bone marrow environment. In one application, this system enables umbilical cord blood (CB) derived hematopoietic stem cells (HSCs) to expand, without differentiating, to proportions large enough for transplantation into adult.

The Company's efforts have been validated by the issuance of U.S. patents that protect the concept and mechanism of action of the PluriX™ 3D bioreactor technology.


 

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