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Home Emerging Technology Stem Cell Research The Science of Stem Cell Research

The Science of Stem Cell Research

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What is a stem cell?


A. Definition

Stem cells are cells that are unspecialized, and through cellular division, give rise to a specific specialized cell, such as a blood or skin cell. In order to be a stem cell requires that the cell possess these two properties:  

1. Self-renewal - the ability to go through numerous cycles of cell division while maintaining the undifferentiated state.

2. Potency - the capacity to differentiate into specialized cell types. Potency specifies a stem cell's potential to differentiate into different cell types.

 There are four different types of potency:

Totipotent stem cells are produced from the fusion of an egg and sperm cell. Cells produced by the first few divisions of the fertilized egg are also totipotent. These cells can differentiate into embryonic and extra-embryonic cell types.

Pluripotent stem cells are the descendants of totipotent cells and can differentiate into cells derived from any of the three germ layers.

Multipotent stem cells can produce only cells of a closely related family of cells (e.g. hematopoietic stem cells differentiate into red blood cells, white blood cells, platelets, etc.).

Unipotent cells can produce only one cell type, but have the property of self-renewal which distinguishes them from non-stem cells (e.g. muscle stem cells).

B. Differentiation

1. Embryonic stem cell lines (ESC) are cultures of cells derived from an embryo at the blastocyst or earlier morula stage. A blastocyst is an early stage human embryo (approximately four to five days old in humans) and consisting of 50–150 cells. ESCs are pluripotent and give rise during development to all derivatives of the three primary germ layers: ectoderm, endoderm and mesoderm. Simply put, they can develop into any of the more than 200 cell types of the human body when given sufficient and necessary stimulation for a specific cell type.
After nearly ten years of research, there are no approved treatments or human trials using embryonic stem cells because of the major health risks they pose to humans.

ESCs, being pluripotent cells, require specific signals for correct differentiation. If they are injected directly into another body, ESCs will differentiate into many different types of cells causing a teratoma (a type of cancerous tumor). Differentiating ESCs into usable cells while avoiding transplant rejection are just a few of the hurdles that embryonic stem cell researchers still face. Due to many debates on the ethical nature of ESCs, many nations currently have moratoria on either ESC research or the production of new ESC lines.

2. Adult stem cells (also known as somatic stem cells and germ line stem cells) are any cells which are found in a developed organism. ASCs have two properties: (1) the ability to divide and create another cell like itself and (2) divide and create a cell more differentiated than itself. They can be found in children as well as adults and are hidden deep within organs, surrounded by millions of ordinary cells. They have been found in several organs that need a constant supply of cells, such as the blood, skin, and lining of the gut, and have also been found in surprising places like the brain, which is not known to readily replenish its cells.

 Unlike embryonic stem cells, adult stem cells are already somewhat specialized. For example, blood stem cells normally only give rise to the many types of blood cells, and nerve stem cells can only make the various types of brain cells. Recent research however, suggests that some adult stem cells might be more flexible than previously thought, and may be made to produce a wider variety of cell types. For example, some experiments have suggested that blood stem cells isolated from adult mice may also be able to produce liver, muscle, and skin cells, but these results are not yet proven.

Pluripotent ASCs are rare and generally small in number but can be found in a number of tissues including umbilical cord blood. A great deal of ASC research has focused on clarifying their capacity to divide or self-renew indefinitely and their differentiation potential.
Some adult stem cells are currently being used in therapies.
ASC treatments have been successfully used for many years to treat leukemia and related bone/blood cancers through bone marrow transplants. Adult stem cells are also used in veterinary medicine to treat tendon and ligament injuries in horses.

The use of ASCs in research and therapy is not as controversial as ESCs, because the production of adult stem cells does not require the destruction of a human embryo. Additionally, because in some instances ASCs can be obtained from the intended recipient (called an autograft), the risk of rejection is essentially non-existent. Consequently, more US government funding is being provided for adult stem cell research.

3. Induced pluripotent stem cells (iPSCs) are a type of pluripotent stem cell artificially derived from a non-pluripotent cell, typically an adult somatic cell. This is accomplished by inducing a "forced" expression of certain genes in the cell. iPSCs are believed to be identical to natural pluripotent stem cells, such as embryonic stem cells, but the full extent of their relation to natural pluripotent stem cells is still being assessed.
iPSCs were first produced in 2006 from mouse cells and in 2007 from human cells.

This has been cited as an important advancement in stem cell research, as it may allow researchers to obtain pluripotent stem cells, which are important in research and potentially have therapeutic uses, without the controversial use of human embryos. iPSCs are typically derived by transfection of certain stem cell-associated genes into non-pluripotent cells, such as skin cells. Transfection is typically achieved through viral vectors, such as retroviruses.

After 3-4 weeks, small numbers of transfected cells begin to become similar to pluripotent stem cells. iPSCs were first generated by Shinya Yamanaka's team at Kyoto University, Japan in 2006. Yamanaka had identified genes that are particularly active in embryonic stem cells, and used retroviruses to transfect mouse fibroblasts with a selection of those genes. Eventually, four key pluripotency genes essential for the production of pluripotent stem cells were isolated.

However, this iPS line showed DNA methylation errors compared to original patterns in ESC lines and failed to produce viable chimeras if injected into developing embryos.In June 2007, the same group published a breakthrough study along with two other independent research groups from Harvard, MIT, and the University of California, Los Angeles, showing successful reprogramming of mouse fibroblasts into iPS and even producing viable chimera.

These cell lines were also derived from mouse fibroblast by retroviral mediated reactivation of the same four endogenous pluripotent factors, but the researchers now selected a different marker for detection. Unfortunately, one of the four genes used is oncogenic, and 20% of the chimeric mice developed cancer. In a later study, Yamanaka reported that one can create iPSCs even without the oncogenic gene. The process takes longer and is not as efficient, but the resulting chimeras didn't develop cancer.

 In November 2007, a milestone was achieved by creating iPS from adult human cells; two independent research teams' studies were released - one in Science by James Thomson of University of Wisconsin-Madison and another in Cell by Shinya Yamanaka and colleagues at Kyoto University, Japan. With the same principle used earlier in mouse models, Yamanaka had successfully transformed human fibroblasts into pluripotent stem cells using the same four pivotal genes with a retroviral system.

The viral transfection systems used insert the genes at random locations in the host's genome; this is a concern for potential therapeutic applications of these iPSCs, because the created cells might be susceptible to cancer. Members of both teams consider it therefore necessary to develop new delivery methods.

C. Positive impact 

Many scientists, such as the famous Ian Wilmut who administered the team that cloned Dolly, planned to pursue human cloning and embryonic stem cell research. However, like Mr. Wilmut, many have since given up on ESC in favor of iPSC research. Jamie Thomson, who was the first to pluck viable cells from a human embryo and grow them in culture, recently took charge of an institute focusing primarily on iPSC research. The reason? Advancements are being made almost everyday in the field of iPSC research, the cells needed to do the research are easily obtainable and there are no moral or ethical quandaries with the methods. 

Recently, researchers at the government-backed National Institute of Advanced Industrial Science and Technology said they created stem cells like those found in human embryos using the removed wisdom teeth of a 10-year-old girl. The scientists used teeth that had been extracted three years ago and had been preserved in a freezer. This means that it is easy to stock this source of stem cells.

Another advancement in the field of iPSC research involves the debilitating and, once thought incurable, ALS (Lou Gehrig’s disease). Scientists at Harvard and Columbia have, for the first time, used the new iPSC technique to transform an ALS  patient's skin cells into motor neurons. This process may be used in the future to create tailor-made cells to treat the devastating disease. The research was published July 31 in the online version of the journal Science. This was the first time that skin cells from a chronically-ill patient have been reprogrammed into a stem cell-like state, and then coaxed into the specific cell types that would be needed to understand and treat the disease.

These examples are just mere scratches on the surface of the huge innovations that have been made in iPSC research in the last year. People who were once paralyzed now walk thanks to adult stem cells. In one study, people who were once completely blind regained some sight from the use of adult stem cells. IPSC’s do not carry the risks of tissue rejection the way embryonic stem cells do either. Cell replacement therapies and fully effective cures may still be years away, but induced pluripotent stem cell technology has proven itself far more successful and ethical than embryonic stem cell technologies.

D. Negative impact (To be added)

E. Biblical perspective (To be added)

F. Legislative Recommendations

The concept of establishing legal Personhood for all humans from fertilization to natural death would create the legal protection needed to stop the experimentation on humans at the embryonic level. Experimentation on embryonic humans is a violation of the Nuremberg Code and of their basic human rights. 




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