Monday, October 29, 2012

What Are Stem Cells?

Stem cells are unique because they combine two key properties: Pluripotency and self-renewal. Pluripotency means that they can differentiate and give rise to multiple different cell types. In addition, they have the ability to divide and self-renew to maintain the original population.

There are two principally different types of stem cells: Embryonic stem (ES) cells and adult stem cells (or tissue-specific stem cells). In addition, induced pluripotent stem (iPS) cells are very similar to ES cells, and are the focus of intense ongoing research and development.

Embryonic stem cells (ES cells or ESC) arise from the fertilization of an egg by a sperm. The first few rounds of division this fertilized egg undergoes create both the extra-embryonic tissue as well as a pool of identical ESC that eventually will give rise to the new individual. The unique ability of ESC to give rise to absolutely all cell types in the body has lead to increased interest in these cells for both basic and medical research. Such research can improve our understanding of normal development and genetic diseases, and also has a potential for development of tissue regeneration therapy. However, there is also controversy in regards to ethical issues when it comes to the use of human ESC.

Researchers have developed a method where mature differentiated cells can be reprogrammed to become immature pluripotent cells, named induced pluripotent stem cells (iPS cells or iPSC). These iPSC are found to be very similar to primary ESC, but are not identical. These cells provide an alternative source of pluripotent cells. iPSC and ESC therefore remain the focus of intense research, both to understand the mechanisms of pluripotency and to improve the method of reprogramming to create iPSC.

The 2012 Nobel Prize in Physiology or Medicine was awarded to Sir John B. Gordon and Dr. Shinya Yamanaka for "the discovery that mature cells can be reprogrammed to become pluripotent" (source: ), further emphasizing the importance of research on reprogramming and induced pluripotency.

Adult stem cells are also referred to as tissue specific stem cells and can give rise to all cell types within a specific tissue. One example is the hematopoietic stem cell (HSC). In adults, most HSC are found in the bone marrow (BM), but can be immobilized into the blood stream for instance for the purpose of HSC transplantation for treatment of leukemia. HSC are pluripotent and give rise to red blood cells, platelets, and all white blood cells required in the immune system. These stem cells alternate between a quiescent (non-dividing, resting) and a proliferative state (undergoing cell divisions), and provide a life-long source of all blood and immune cells for the individual.

The self-renewal property is crucial for life-long replenishment of the downstream cell types. Exhaustion (or defective self-renewal) of stem cells will lead to disease. For instance, an exhaustion of the HSC, which give rise to all blood cells, will lead to anemia and immunodeficiency. Anemia is the reduction of red blood cells that are crucial for oxygen transport. Immunodeficiency is a defect in any immune cell that is required to protect your body against infection, damage and cancer.

However, the property of self-renewal is also potentially dangerous, as uncontrolled self-renewal is a key feature of cancer cells. Thus, in healthy stem cells, as well as other diving cells, self-renewal is tightly regulated. A critical combination of mutations can lead to loss of this regulation and give rise to cancer. Control of self-renewal is also a major concern and challenge that scientists face in regards to the potential use of ESC or iPSC for tissue regeneration therapy.