A Triumph for Stem Cell Research

Although the potential applications of stem cell therapy are numerous, right now some of its most promising conceivable uses are in the treatment of degenerative brain disorders, such as Alzheimer’s disease (AD) or Parkinson’s disease (PD). In both of these afflictions, essential brain regions deteriorate, leading to notoriously debilitating symptoms. In AD, cholinergic neurons are depleted, while a loss of dopaminergic neurons is responsible for the effects of PD. Some scientists see disorders like these as ideal cases for stem cell treatment. For, in theory, if cholinergic or dopaminergic neurons are deteriorating, one could implant stem cells into the brain of the patient that could then be prodded to form new neurons. This could offset the atrophy caused by the disease.

Thus far, attempts to do this in laboratory animals have had mixed results. Sometimes a slight improvement can be seen, lending credence to the potential validity of the procedure. But failure for a diseased animal to get better after stem cell injection is more common, indicating there are problems with the technique. It is thought that those problems may have to do with the genetic compatibility of the stem cells being implanted into the subject’s brain and the subject's immune system. Perhaps the immune system is recognizing the stem cells as foreign and initiating a response to destroy them. This could be responsible for the animal’s lack of improvement.

Any scientists in training might want to pause for a moment before reading on and try to think about a logical solution to this problem. If a mouse’s immune system is rejecting stem cells from another mouse, what is a way to get around this?

The answer is: use stem cells genetically identical to the subject mouse’s cells. A group of researchers at Memorial Sloan-Kettering Cancer Center induced PD in mice by injecting them with a toxin. They then took skin cells from the tails of the mice and did a little DNA switcheroo. They took the DNA out of the skin cells and transferred it into mouse egg cells that had already had their own DNA extracted from them. The group then prodded the egg cells to divide, eventually producing stem cells as a part of normal embryonic development. The researchers added the appropriate growth factors to the stem cells to cause them to differentiate into brain cells.

They then injected the newly formed brain cells into the PD mice. The immune systems of the mice recognized the brain cells as “self”, since they were genetically identical. Thus, no immune response was mounted, and the mice showed significant neurological improvement. Out of about 100,000 genetically similar brain cells injected into each PD mouse, approximately 20,000 cells survived to function in each brain. Of course the study also had a group for comparison that received genetically dissimilar cells, and these mice did not get healthier. Only a few hundred of the genetically different cells survived in the brains of the mice in this group (of the same number injected).

This is what stem cell researchers have been waiting for: the use of somatic cell nuclear transfer (cloning) technology to make replacement cells for the body, resulting in clear evidence that it can lead to significant recovery from degenerative disorders. It is vindication for those who have been proclaiming the limitless possibilities of stem cells.

It, however, does not get around the fundamental problem stem cell advocates face. It requires the use of embryonic cells to create the stem cells. Thus, despite the potential it has, it will continue to face harsh political opposition. One has to hope, however, that as these procedures become perfected in organisms like mice, opponents will have to adopt a more utilitarian perspective. Perhaps using some of the half a million frozen embryos that are collecting dust in the in vitro fertilization clinics across the country would be considered a little more in depth if their ability to alleviate the suffering of living PD sufferers, which number over a million in the U.S. alone, had been demonstrated repeatedly in animal studies.

For other posts from me on stem cells, go here or here.

Sisyphus and Science, or History Repeats Itself

Researchers working at the Harvard Stem Cell Institute (HSCI) published a paper online last week in Cell Stem Cell discussing advances they’ve made in trying to coax adult cells to revert to embryonic stem cell-like states, without viruses or oncogenes (cancer-causing genes). They have outlined the molecular process involved in this nuclear reprogramming, something which up until now has been a very nebulous sequence of events. Being able to reprogram cells without viruses or oncogenes is crucial, as their involvement prohibits the use of the resultant embryonic stem cells (ESC) in humans.

While it is important to understand this process, a great amount of time and research money is being spent trying to convert adult cells to ESCs when there are somewhere around ½ a million frozen embryos sitting in fertility clinics around the country. When a woman undergoes in vitro fertilization (IVF), several embryos are created from the fertilization process. After a few days, the embryos are inspected and the healthiest few are selected for transfer (the actual number transferred varies with the age of the patient and the laws of the country where the procedure is done). The patient can then decide what to do with the remaining embryos: freeze (cryopreserve) them, donate them to research, or dispose of them. Many patients, thinking of the potential for life (or for future IVF procedures) the blastocysts possess, have an understandably difficult time making the decision to donate them to research or have them disposed of (for an interesting article on the difficulty of this decision, go here). Thus, the embryos are frozen and there they stay, sometimes indefinitely.

But, due to George W. Bush’s fanatical opposition of stem cell legislation, scientists can’t get research funding from the government to use even those frozen embryos that patients have chosen to donate to science. They remain untouched, alongside the hundreds of thousands of others, as the top scientists in the country try to figure out ways to make ESCs out of adult cells.

Ironically, IVF itself was the focus of political and ethical debates for years, attacked with the same arguments being used against ESC research. Now, however, it is a commonly accepted practice. And, while IVF provides infertile couples or women with the ability to have children—an amazing blessing for these people—ESCs have potential to be used in the treatment of any disease that involves the degradation of tissue. This would include Parkinson’s, Alzheimer’s, type I diabetes, spinal cord injuries, or stroke (to name a few). Thus, ESCs might be able to provide some blessings of their own.

While the advancements of the researchers at HSCI are great, I can’t help but wonder what type of developments we would be seeing if scientists didn’t have to focus on this hurdle of turning adult cells into ESCs, when there are hundreds of potential ESC lines just waiting out there to be created from frozen embryos. It’s like being tied down to a chair in the middle of the grocery store and dying of starvation.

Stem Cells and the Brain

Stem cells are probably one of the least understood (by the public), yet most fascinating, biological entities we have identified. Who of us hasn’t marveled at the ability of a newt to grow back its limbs after they are cut off, or of a starfish to be cut in half and regenerate to form two new starfish? Both organisms are able to do these seemingly miraculous things because of stem cells. So you can understand why some scientists are consumed with understanding and utilizing stem cells, in the hopes of slowing disease and even aging. Stem cells are special because they are versatile cells that can be prodded to develop into any type of adult cell, be it muscle, liver, nerve, etc. This makes them valuable not only for possible cell replacement therapies (for degenerative diseases like Parkinson’s), but also for the study of cell growth to learn more about the etiology of disease. If you are unfamiliar with stem cells and have a few hours to learn about them, there is a fantastic series of lectures available for free on the Howard Hughes Medical Institute’s interactive site, http://www.hhmi.org/biointeractive/lectures/.

Manipulating stem cells, however, is not easy and involves several dilemmas. A major one is: once you have one of these versatile cells, how do you get it to become what you want it to be? This is an area of continuing research, and in most cases involves finding a gene or set of genes responsible for directing the stem cell’s growth. This, once again, is not an easy task, as there are somewhere around 30,000 genes in a human cell (estimates vary).

Occasionally, however, there are successes. Dr. Edwin Monuki and colleagues at the University of California, Irvine, have identified a gene called Lhx2 that directs stem cells in early development to form the cerebral cortex. The cortex is responsible for higher-order functions in humans, such as reasoning, language, and vision. Degradation of or damage to the cortex can be very debilitating, as is seen in cases of Alzheimer’s disease or stroke. Thus, the discovery of a mechanism to turn stem cells into cortical cells has great potential to slow neurodegenerative disease or help patients recover from cerebrovascular accidents. Despite the political controversies, stem cells are one of the most promising tools we have for fighting disease and aging, although much more must be learned about them before they can fulfill our expectations. Discoveries like Dr. Monuki’s are edifying steps toward that goal.