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What Are Stem Cells?

What are stem cells?
Are there different types of stem cells?
Where do stem cells come from?
What are embryonic stem cells?
What is a cell line?
If stem cells are immortal, why do we need more cell lines?
What are adult stem cells?
Are adult stem cells any better than embryonic stem cells?
Can scientists turn non-insulin producing cells into islets?
What about umbilical cord cells?
Why are Mesenchymal Stem Cells (MSCs) a valuable resource?

What are stem cells?
Stem cells are immature cells that have not yet determined their developmental direction. These cells have the remarkable potential to develop into many different cell types in the body. Serving as an internal repair system, these cells can theoretically divide without limit to replenish native or damaged cells for as long as the person or animal is still alive. When a stem cell divides, each resulting cell has the potential to either remain a stem cell or become another type of cell with a more specialized function, such as a muscle cell, a red blood cell, a brain cell, or even an islet cell.

Are there different types of stem cells?
There are three types, or classes, of stem cells: totipotent, multipotent, and pluripotent.
Totipotent -- cells produced from the fusion between an egg and a sperm that can develop into a living embryo
Multipotent -- cells that can give rise to a small number of different cell types. Example: adult stem cells.
Pluripotent stem -- cells that can give rise to any type of cell in the body, but cannot develop into an embryo. Example: embryonic stem cells.

Where do stem cells come from?
Pluripotent stem cells are taken from blastocysts, which are embryos at the earliest stage of development – only a few days old. Cells from these embryos can be used to create pluripotent stem cell "lines" — cell cultures that can be grown indefinitely in the laboratory. Pluripotent stem cell lines have also been obtained from more developmentally advanced stages (for example, embryonic germ cells), but have received only limited attention. 

In the last five years, we have witnessed the development of a third type of pluripotent cell: induced pluripotent cells (IPCs). These are the result of man-made reprogramming of adult cells and could potentially be derived from any individual.

What are embryonic stem cells?
Embryonic stem (ES) cells are the most powerful and best studied stem cells available. Once in culture, ES cells proliferate at a remarkable speed. In just a little longer than three weeks, a thousand of these cells will have generated more than a billion more, enough to transplant two type 1 diabetic patients, provided that we could efficiently differentiate them into beta cells.

    Harnessing the power of these cells, however, is challenging. Some of the challenges that undermine the ES cells’ potential include:
  • Difficulties in harvesting and cultivating
  • Severely limited genetic diversity
  • Outdated cell culture methods for their differentiation
  • The likelihood for malignant tumor formation in cells that remain undifferentiated. (When allowed to spontaneously differentiate, ES cells can and will give rise to many different cell types.)

What is a cell line?
A "line" is a culture of stem cells that arises from a unique and defined source. When scientists take a blastocyst and culture embryonic stem cells from it, that culture becomes a cell line. Each one of the cells, and the subsequent cells it gives rise to, shares the same genetic information. Each one of the human ES cells available today comes from a different blastocyst. They are, therefore, unique.

If stem cells are immortal, why do we need more cell lines?
While it is true that ES cells are immortal, there are several reasons why scientists believe that research should not be restricted to the cell lines originally approved in 2001 for federal funding.

Not all human ES cells are similar. Only a handful has been extensively characterized. The rest are largely useless due to poor manageability, limited undifferentiated proliferation, genetic abnormalities or lack of extensive differentiation potential. In fact, the majority of the scientific reports on human ES cells over the last few years have focused on fewer than ten lines. The need for more ES cell lines is clear even for research purposes only.

What are adult stem cells?
Adult stem (AS) cells are "mature" stem cells that reside in the body throughout adulthood and can be obtained from umbilical cord blood, the placenta, amniotic fluid surrounding the fetus inside the womb and the endometrium, among many other tissues. Because of their capacity to differentiate towards several tissues, adult stem cells are known to be multipotent.

Despite their limited growth potential, adult stem cells generally do not have the potential for malignancy, are harvested with relative ease, and are available in greater supply.

Are adult stem cells any better than embryonic stem cells?
Over the last few years, many reports have shown that stem cells isolated from several adult tissues show unexpected pluripotency. Traditionally, the interest of such observations has been somewhat diminished by the fact that these cells rarely proliferate in culture for extended periods. This property (proliferation potential) is critical for the scalability of any research protocol onto therapeutic applications.

Recent studies have suggested that adult stem cells derived from bone marrow have the capacity to differentiate in much the same way as that of ES cells, and can also expand indefinitely in culture. The potential to obtain these cells from a patient, then expand or "grow" them and selectively induce their differentiation into the required cell type (for instance, islets), would be the treatment of choice for the replacement of damaged tissues. However, these studies could not be replicated by other laboratories. More recently, amniotic fluid stem cells have been shown to share some ES cell properties (see section ahead). Additional studies, however, are necessary to ascertain these claims.

Can scientists turn non-insulin producing cells into islets?
When ES cells develop, they go through a natural process of maturation by which they differentiate into any particular, specialized cell type, such as beta cells. In addition to research aimed at reproducing these steps and encourage their development into islets, scientists are also looking at ways to circumvent this complex natural developmental process by converting mature cells, like liver or pancreatic exocrine cells, into insulin-producing cells.

During this process, called trans-differentiation, no maturation occurs. Trans-differentiation takes place very rarely in nature, but can be achieved in the lab under defined culture conditions and/or by genetic, RNA or protein manipulation. Some theorize that bona fide trans-differentiation requires the de-differentiation of an adult cell type so that it can now mature in another direction.

The best example of de-differentiation is "reprogramming."  In this case, an adult cell type is reprogrammed by forcing the expression of key master genes that will make the cell "go back in time."

What about umbilical cord cells?
Umbilical cord blood cells are showing promise as a new source of insulin-producing cells and as a potential donor-specific tolerance technique that thwarts immune attacks by re-educating the immune system to accept donor and recipient bone marrow cells as "self".

Cord blood stem cells, as the name implies, are derived from newborn umbilical cord blood. The umbilical cord harbors two types of stem cells: mesenchymal and hematopoietic. Mesenchymal cells potentially could be used as immunomodulators and "helper" cells in the process of endogenous regeneration. Hematopoietic cells are similar to those obtained from the bone marrow, and their primary purpose is to generate the entire array of blood-forming and immune cells. Both cell types are being actively investigated for their potential to reeducate the immune system in Type 1 diabetes.

Why are Mesenchymal Stem Cells (MSCs) a valuable resource?
Mesenchymal Stem Cells are multipotent “self-repairing” stem cells typically found in the bone marrow, but also in other tissues like the fat. MSCs can transform into a variety of connective tissue types and are easily cultured, making them good candidates for tissue repair. Their anti-inflammatory and tissue regeneration properties are currently being studied.

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Learn more about the development of the BioHub mini organ to restore natural insulin production in those living with diabetes.
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