What Matters: March 2005
Stem cells: The Potential and the Pitfalls
By Erin Lavik '95, SM '97, ScD '01
I started working with stem cells through a circuitous route. Part of the way through graduate school, I changed fields and began to work on developing a new approach to trying to treat spinal cord injury. There is a whole cascade of events that occur following spinal cord injury which lead to the loss of neurons, the cells that carry the signals in the nervous system, as well as the glia, the cells that support the neurons. As part of my approach, I wanted to replace these cells that were lost.
Glial cells can multiply, so it was reasonable to think that a few might be able to be harvested, expanded, and reintroduced to assist in repairing the tissue. Neurons are not so easily expanded. As I was trying to find a source for cells, I went to a conference in which several neural stem cell researchers spoke about their work. The cells could not only multiply indefinitely, they seemed to understand the injury, and replace the particular cells that were lost—both the neurons and glia and had the potential to restore function.
Perhaps. In my graduate work, though, the cells did not survive in large numbers and did not replace the cells lost in the injury. Survival of transplanted cells of any type is a real challenge in the field. Getting surviving cells to function properly is a second challenge. Early data suggests that stem cells survive and integrate better in many injury and disease models, but the number is often lower than thought to be therapeutically beneficial.
What is a stem cell?
The only cells that have been shown to be stem cells in a truly rigorous manner are hematopoetic stem cells. These cells are extracted from bone marrow, capable of being expanded indefinitely, and capable of replacing all of the cells of the blood which one cannot do with other kinds of stem cells because one cannot eliminate the nervous system or other tissues and survive long enough to replace them. With stem cells drawing so much attention and potential funding opportunities, many cells that were once referred to as progenitor cells or stem-like cells had their names changed. Now, I go to conferences where cells that wouldn't have even been considered progenitors, much less stem cells, five years ago are referred to as stem cells.
Since I first encountered stem cells, other varieties have emerged. Mesenchymal stem cells have been isolated and publications suggest that they can not only be directed into the cells of the structural tissues such as bone, muscle, and tendon, but they may be able to also become neurons. This would be brilliant. Transdifferentiation, if true, might mean that one could do a marrow biopsy, isolate the stem cells, and direct them to become neural tissue. From the point of view of development, however, this is a long shot. A cell must dedifferentiate to a less mature cell and then differentiate to a more mature one in a different pathway. Though attractive, transdifferentiation has not been shown conclusively and not for every cell one might need.
An alternative might be to start with a cell that is more immature and doesn't need to dedifferentiate. The cell farthest back in this stream is the embryonic stem cell. All the rest of the cells of an organism are derived from it. Mouse embryonic stem cells have been around for over 20 years. Scientists are still trying to determine their potential for therapies. Human embryonic cells were first isolated in 1998. We know that they can become every kind of cell a person would need. What we don't know is whether we can direct them to become the cells needed at a particular point in time and be functional. If we want to know, we will have to study a great number of lines that have been isolated in different manners and expanded for different lengths of time because the isolation, culturing, and expansion are variables that have huge effects on stem cell behavior.
We cannot talk about the potential of stem cells without an awareness of the ethical and political considerations. Likewise, though, we cannot address these issues without an understanding of the science of these cells. Over the last year, the United States Conference of Catholic Bishops (USCCB) has released advertisements regarding the use of human ES cells. One of these advertisements states that, "Stem cells in our bodies work wonders....They've helped people with severe spinal cord injuries to walk again....They are adult stem cells obtained without harming anyone." As someone who works with stem cells and progenitors for spinal cord injury, I was quite startled to hear this. So, I did some research. It seems that the cells described here are those used in a small spinal cord trial in Portugal by Dr. Carlos Lima and his colleagues. Patients in the trial have described some improvements after the surgery which involves clearing out scar tissue and introducing olfactory cells, but in the absence of controls, it is impossible to know if the improvement is due to the surgery or cells.
Why study stem cells?
If one can cure an injury without cells, why study stem cells at all? Part one of the answer is that there are times when too much tissue is damaged. In the case of Dr. Lima's study, all of the patients appear to have sustained contusion injuries and, while paralyzed, they maintained some feeling and function below the site of the injury suggesting that some of the connections were still functional. Unfortunately, this is often not the case. In these cases, some researchers hope that stem cells may provide a means to make new connections. Beyond spinal cord injury, there are diseases in which a particular cell type is lost and scientists hope that stem cells may provide a means to replace those cells and restore function.
We do not know what cells will be able to repair different tissues. Neither adult nor embryonic human stem cells have helped people with severe spinal cord injuries to walk again. In fact, neither cells have had any statistically significant, documented impact at this point on spinal cord injury in humans.
On September 29, 2004, a spokesman for the USCCB spoke before the Senate Commerce, Science, and Transportation Committee stating that "American scientists and others dazzled by visions of technical progress have always been tempted to endorse a utilitarian approach to ethics and to treat helpless or unpopular members of the human race as mere means to their ends." It is dazzling to think that one day spinal cord injury would not be permanent. Whether stem cells play a role remains to be seen. There is a lot of work that is needed, and it needs to be done not with a utilitarian view of ethics or a disregard for the human race but with the greatest respect and the most rigorous science. In the meantime, it is the responsibility of each of us, independent of our moral views, to understand the data and not misrepresent or exaggerate results to support our own views. That data represents part of the human race trying to find a cure.
About the Author
Erin Lavik '95, SM '97, ScD '01, assistant professor of biomedical engineering at Yale University, earned her MIT degrees in materials science and engineering. Her research focuses on developing new therapeutic approaches for the treatment of spinal cord injury and retinal degeneration.
What Matters is a guest opinion column written by a different MIT alumnus or alumna. The views expressed are entirely those of the author and do not necessarily represent the views of the Alumni Association or MIT. Interested in writing a column? Email whatmatters@mit.edu.
