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Stem Cell Breakthroughs: What Do They Mean for Parkinsonís?

Stem cells are often touted for the potential they hold to treat diseases, including Parkinson’s disease (PD). So, when a new development in stem cell science is referred to as a ‘breakthrough,’ you may wonder what the true implications are for PD treatments.

Since the last issue of News & Review, two studies have been published, each highlighting an alternative source of stem cells. In November 2007, scientists announced they had created stem cells by reprogramming human adult skin cells. More recently, on January 17, researchers at the Stemagen Corporation announced they had been successful in using adult skin cells to clone embryos.

What do these results truly mean for research funding, for governmental policy and, most importantly, for the development of treatments that may affect people living with PD?

Why are Stem Cells Important?

Researchers see promise in stem cells because of their ability to become any type of cell in the body. They foresee manipulating stem cells to create specialized cells that may be used to replace the cells or tissue damaged or destroyed by disease — such as the unhealthy or missing cells that are found in diseases such as Parkinson’s, diabetes, and Alzheimer’s.

In the case of Parkinson’s, this would entail manipulating stem cells into dopamine-producing neurons and using these to replace the cells that are lost in PD.

Prior to these recent developments, scientists looked to human embryonic stem cells (hESCs) as the most ideal type of stem cells for disease research and treatment development because they are the most versatile of stem cells. This is both because their structure allows them to transform into any type of tissue in the body and because they can be easily multiplied. The ability to multiply allows researchers to develop stem cell lines, groups of cells that make research much easier to perform.

Conversely, neither adult stem cells nor stem cells derived from cord blood have these abilities. Stem cells from these sources are more difficult to study and to translate into treatments.

Stem Cells Derived from Skin Cells

In November 2007, reports published in the prestigious journals Science and Cell, led respectively by Dr. Junying Yu, working in the lab of stem-cell pioneer Dr. James Thomson of the University of Wisconsin-Madison, and Dr. Shinya Yamanaka of Kyoto University, announced the successful creation of stem cells through the manipulation of human adult skin cells. With these accomplishments, both teams have created the first stem cells that have the same potential as human embryonic stem cells, but which do not require the use of human embryos.

Why is This a Breakthrough and What Does It Mean for Disease Treatments?

Scientifically, skin-derived cells are important because they hold potential similar to that of hESCs. That is, they are easily replicated and they have the ability to develop into any type of cell in the body. Therefore, skin-derived stem cells hold the potential to develop into cell replacement and tissue therapies — the same treatments that researchers have hoped to develop from hESCs.

Since skin-derived cells can be taken from adults who have a particular disease, they also open up the possibility of growing replacement tissue in a lab that is unique to the person who is being treated. Having a customized therapy of this kind could eliminate the concern about immune system rejection that comes with hESCs.

The discovery of skin-derived stem cells will have political and financial ramifications as well. Because the source of these cells is something other than a human embryo, the research will not be subject to the same constraints that were set by President Bush in 2001 for hESCs. These regulations limit federal funding for human embryonic stem cell research to lines developed before August 9, 2001. The rules essentially require institutions to house stem cell research in separate facilities, using separate equipment, from research funded by the government — creating a burden for institutions in terms of cost, logistics and liability. This problem was compounded by the fact that the available stem cell lines turned out to be many fewer than was originally thought and not always of the high quality necessary for research. Such issues have discouraged institutions and researchers from entering the field.

However, because stem cells derived from skin cells do not involve embryos, they bypass all of these regulations, meaning they will be eligible to receive federal funding. In fact, the President has already moved to encourage funding of research involving skin-derived cells, as evidenced by his statement in the State of the Union Address on January 28.

With the possibility of increased funding present and the belief of scientists that skin-derived stem cells can be easily and quickly replicated at institutions across the country, it is hoped that the sheer increase in the amount of research that can be performed will speed scientific progress.

What Scientific Barriers Still Exist in Developing Treatments?

While skin-derived stem cells appear to offer the same flexibility and potential as hESCs, they also possess some of the same inherent limitations as their predecessors, along with some new ones.

For instance, when hESCs are developed into treatments, they are able to transform again within the body. In cases where this proliferation is uncontrolled, the result can be the development of tumors (known as teratomas) in people being treated with stem cell therapies. Scientists have not yet figured out how to prevent this from happening, whatever the source of the stem cells.

In addition, skin-derived stem cells cannot be used as actual treatments as they currently exist because the process that transforms them into stem cells involves injecting them with viruses that could be harmful to patients.

Scientists Use Adult Skin Cells to Create Cloned Embryos

On January 17, researchers from Stemagen Corporation led by Andrew French, Ph.D., published a study in Stem Cells announcing that they had created five human embryo-like structures and brought them to the blastocyst stage by using somatic cell nuclear transfer (SCNT) — also known as therapeutic cloning.

These results represent the first time that a research team has brought a cloned embryo to the blastocyst stage. This is the point at which stem cells can be produced, although this study did not proceed far enough to do so.

Why is This a Breakthrough and What Does It Mean For Disease Treatments?

Because the study did not yet produce stem cells, its findings do not mean that the development of treatments is right around the corner. However, the approach is certainly promising.

The team, using the SCNT technique, took adult skin cells from two of the researchers and eggs (oocytes) donated from women who were undergoing fertility treatments at a nearby clinic. Following SCNT protocol, researchers removed the nuclei from adult skins cells and placed them within the donated eggs, whose own nuclei (and therefore, DNA) had been removed.

Through the use of this technology, the scientists were able to manipulate the eggs into becoming embryos containing the genetic material of the adult skins cells. Out of 25 eggs, researchers produced three blastocysts that were proven to be clones, meaning the blastocysts genetically matched the parent cells taken from the researchers.

If stem cells had been developed using this process, then, like skin-derived stem cells, they would have had the potential to lead to cell replacement and tissue therapies. Moreover, because the cells produced in this way would be genetically-matched to the donor, they could potentially be used as personalized treatments for diseases like Parkinson’s.

Researchers hope to one day use SCNT technology — taking body cells from an individual with a disease along with donated eggs — to create an embryo-like structure that carries a person’s own DNA. Unlike cells derived from other sources, the stem cells created from SCNT would be recognized as ‘self’ not as something for the immune system to attack.

What Scientific Barriers Still Exist in Developing Treatments?

Before proceeding to the development of treatments, researchers must first go one step further by yielding actual stem cells from the blastocyst stage and subsequently growing them into lines to be studied. Developing the stem cells into treatments for Parkinson’s will require further investigation. In addition, the health of the embryos created in the study will need to be assessed and verified by outside groups.

Conclusions

Overall, while important scientific challenges continue to exist with respect to stem cells derived from skin cells and from therapeutic cloning, these newly-discovered technologies provide the opportunity for researchers and institutions to explore more deeply the potential of stem cells to cure human diseases.

Although this research is exciting, scientists emphasize that studies involving human embryonic stem cells should continue in tandem with new techniques. Together, further research on stem cells from all sources will speed our understanding of disease and of possible treatments.