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Stem Cell Initiative
stem cell initiative
| Stem Cell Exploration: Scientists Investigate Brain, Heart, Skin |
—All stories by Pat Olsen
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| Fiona Doetsch, PhD |
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Photo: Eileen Barroso
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When Fiona Doetsch, PhD, peers at brain stem cells through a microscope, it’s always magical. “There’s something amazing about seeing unexpected patterns of glowing cells deep inside the brain that reveal insights into how the brain works,” says Dr. Doetsch, assistant professor of pathology and cell biology, neurology, and neuroscience.
That stem cells even exist in the brain is a recent revelation. For a long time scientists believed that people were born with a finite number of neurons in the brain that died off over time. But about 10 years ago, a new era in neuroscience began when scientists discovered that two parts of the brain, the hippocampal formation and the subventricular zone (SVZ), continue to generate neurons throughout life.
“The discovery of these new neurons was fascinating. If neurons are born throughout life, then there should be stem cells creating these new neurons,” Dr. Doetsch says. “And if these stem cells can be precisely targeted in vivo, it may be possible to direct them to make new replacements for people who have lost brain cells, as in stroke, Parkinson’s disease, multiple sclerosis, or other neurodegenerative diseases.”
But first the stem cells had to be identified. The brain has both neurons and glial cells, and scientists initially thought that there were progenitor cells restricted to creating neurons and different progenitors restricted to producing glia.
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| Blood vessels next to neural stem cells (in blue) appear to help control the production of new neurons in the brain, according to Fiona Doetsch’s latest research. Contact with blood vessels could ease the delivery of drugs that stimulate the cells to make repairs. (photo courtesy of Fiona Doetsch) |
Neural stem cells are special, but so is the brain region in which they reside. Astrocytes are spread throughout the brain, but new neurons are generated only in the SVZ and hippocampus. Are astrocytes in other parts of the brain prevented from generating neurons because they are in a different environment? Or are neural stem cells special types of astrocytes?
Dr. Doetsch’s findings suggest the environment plays a big part. Her team recently found that the SVZ’s vasculature is a key component controlling the lives of stem cells. Stem cells are often found in direct contact with blood vessels at specialized sites and divide most frequently at these sites. Combined with an unusual blood brain barrier the team discovered in these regions, Dr. Doetsch speculates that the arrangement may make the stem cells more accessible to drugs and facilitate the stimulation of the brain’s own stem cells for repair.
“In the past decade we have learned that the brain has an unexpected ability to change and respond dynamically to its environment,” Dr. Doetsch says. “That gives me hope that we will soon have a new understanding of brain function and, eventually, new treatments.”
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| Warren Sherman, MD |
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Photo: Cardiovascular Research Foundation
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For many diseases and disorders, stem cell therapy may lie 5, 10 or 20 years off in the future, if it materializes at all. That’s a stark contrast with stem cell-related repair and regeneration of the heart, which has already moved into clinical trials.
“We’ve moved beyond the infancy stage of this research fairly quickly,” says Warren Sherman, MD, associate professor of clinical medicine and director of cardiac cell-based endovascular therapies at the Center for Interventional Vascular Therapy. “Many of the effects being observed in patients are positive, and there’s much reason for hope.”
Dr. Sherman currently directs a number of clinical trials that are exploring this new frontier in cardiovascular disease.
“Stem cells have the capacity to either augment the heart’s function or to prevent further deterioration,” Dr. Sherman says. “Many types of cells stimulate the growth of new, “micro” coronary vessels, while others can serve as replacement cells for muscle lost to various diseases.”
In one of Dr. Sherman’s trials, patients suffering from congestive heart failure receive a specific type of adult stem cell, derived from a muscle in the leg, that may add new strength to their hearts. Thus far, studies suggest that a single application increases the pumping capacity of the heart by 5 percent to 10 percent. “Though this may not sound like much,” Dr. Sherman says, “small increments such as these may provide significant benefits to patients when added to standard medical care.”
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| Warren Sherman pioneered the use of catheters to deliver stem cells straight to damaged areas of the heart. The stem cells may repair damage from heart attacks and other diseases by creating new blood vessels or heart muscle. (photo courtesy of Warren Sherman) |
“Patients with the last condition have advanced coronary disease but without having sustained serious heart attacks or developed heart failure. Their burden is quite different: chronic chest pain that limits the simple, daily activities and impacts the quality of their lives. Most have undergone numerous stent procedures and bypass surgeries without lasting relief and have only medications to allay their symptoms,” Dr. Sherman explains.
Dr. Sherman is optimistic that stem cell therapies will help such patients soon. “What we are seeing now is a remarkable expansion of scientific investigation in the field, at every level, with so much of it centered here at Columbia. It has taken many decades for cardiovascular disease to achieve the unfortunate distinction of being the nation’s No. 1 cause of suffering and death. It has taken scientists less than one decade to demonstrate the positive potential of stem cells. If we continue along the path of careful, collaborative research, it would not be extreme to suggest that the first approved stem cell-based therapy will be available to patients with cardiac disease in two to five years. When taken in perspective, it’s quite an extraordinary timeline.”
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| David Owens, PhD |
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Photo: Eileen Barroso
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As someone who knows the dangers of sun exposure, David Owens, PhD, prepares for a day at the beach by applying sunscreen before he leaves the house. But the Irving Assistant Professor of Dermatology and Pathology has an even deeper interest in skin – Dr. Owens hopes his research will one day uncover a link between skin cancer and the skin’s own stem cells.
The numbers are alarming. “Around 2 million cases of skin cancer, mostly non-melanoma, are diagnosed every year, and the American Cancer Society estimates that another million cases go unreported,” Dr. Owens says. Although non-melanoma skin cancer has been actively studied, surgical excision still remains the only treatment for these lesions.
Better treatments for non-melanoma skin cancers will come when researchers identify the skin cells that give rise to the tumors. It’s a good bet that these cells are the skin’s stem cells, since all other epidermal cells only live for about four weeks. “Other cells are simply not around long enough to accumulate the amount of DNA damage needed to transform a normal cell into a cancerous one,” Dr. Owens says.
Skin researchers, however, are still trying to identify all the skin’s stem cells. Last year Dr. Owens’ team discovered a previously overlooked population of epithelial progenitor cells residing in the hair follicles. The cells have the potential to create skin, hair, and sweat glands, but may not sustain all types of cells in vivo under normal conditions. “We’re in the early phases of characterizing what these cells do, what part of the skin epithelium they support, and if they give rise to squamous cell carcinoma, the most dangerous type of skin cancer after melanoma,” he says.
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| Stem cells in the skin's hair follicles, recently discovered by David Owens, may give rise to certain types of skin cancer or new ways to treat skin diseases. (photo courtesy of David Owens) |
Ultimately, Dr. Owens hopes that his research into epithelial stem cells and skin cancer may also improve treatments for other types of epithelial malignancies, which are responsible for 85 percent of all cancers. “Epithelial cells exist not only in the outer layer of skin, but also in the lining of other organs like the colon, lung, and kidney,” he says. “What happens on the body’s exterior may shed light on similar processes deep beneath the surface of our skin.”
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"Our hope is that identifying genes unique to these stem cells will lead to new treatments for skin diseases, cancer, or wound repair.”
DAVID OWENS |
