Stem Cell for Brain Damage or Injury: Swedish Research Results

Stem cell for brain damage or injury: Swedish study offers hope. If cancer is feared for the intense and chronic pain it brings, strokes and neurodegenerative disorders are feared because these ailments are “mind-robbers” — they steal away patients’ minds, taking away their memories, their ability to think and concentrate, and even do simple things like tie their shoelaces or feed themselves.

Strokes happen when blood-flow to a part of the brain stops suddenly in what’s often called a “brain attack.” In that few seconds that the brain can’t get oxygen, brain cells die, causing permanent damage.

With rehabilitation services, stroke survivors regain the feeling in their paralyzed limbs and can begin to walk around and care for themselves. But most of them can never go back to work. They can’t concentrate, can’t work with figures, and can’t write a letter properly, much less deal with complex workplace issues.

Strokes are thus not only a leading cause of death, but the very top leading cause of long-term disability in the United States and the rest of the world. Each year, about 15 million people across the world suffer stroke — about 795,000 Americans. Of these, five million die and another five million are permanently disabled.

Alzheimer’s disease and Parkinson’s disease don’t occur suddenly like strokes, but instead steal upon people slowly and gradually. Nevertheless, they are diseases that are just as terrible — causing a lot of mental pain.

Both progressive brain disorders are leading causes of dementia. Alzheimer’s and Parkinson’s cause sufferers to lose their memories, language skills and perception of time and space — and the loss is irreversible. Eventually, patients can’t even take care of themselves. People with either of these two neurodegenerative diseases also often suffer clinical depression, anxiety and personality changes.

Like Alzheimer’s, Parkinson’s doesn’t involve a lot of physical pain but causes a lot of mental suffering. On top of the dementia and mental pain it has in common with Alzheimer’s, Parkinson’s also involves trembling arms and legs, muscular rigidity and poor balance.

Both brain diseases take their toll on both the patients themselves — as well as those who love and care for them. Sufferers often feel great frustration and fear as they struggle with everyday tasks and slowly lose their independence. Caregivers tend to get burned out while friends and family find it painful to witness how the disease takes their loved one away from them, bit by bit.

Right now, nothing can stop the awful advance of both diseases — there’s yet no cure for either condition, even when these affect millions of people worldwide. About 5.4 million Americans — and 30 million people across the world — suffer from Alzheimer’s. About 7.5 people worldwide live with Parkinson’s — 1.7 million in China, one million in the U.S., about 100,000 in Canada and 1.2 million Europeans.

New stem cell in adult brain discovered
But a new discovery by Swedish scientists bring hope that treatments for strokes and neurodegenerative disorders may be just around the corner. Researchers from Sweden’s Lund University led by a Swedish neuroscientist at the Van Andel Research Institute (VARI) have discovered a new form of stem cell in the adult brain.

The discovery, the researchers enthuse, could lead to developing methods to heal and repair brain injury and disease. Their findings are published in the April 16 issue of the peer-reviewed journal, Plos One.

Analyzing brain tissue from biopsies, the Lund investigators found — for the first time — stem cells located around small blood vessels in the brain. The researchers found that these cells can proliferate and form several different cell types — fat, cartilage and bone cells — and most importantly, glial cells and immature brain cells.

“A similar cell type has been identified in several other organs where it can promote regeneration of muscle, bone, cartilage and adipose tissue,” explains Dr. Patrik Brundin, a Swedish neuroscientist who heads the Neuronal Survival Unit at Lund University and who is the study’s senior author.

But Dr. Brundin and his colleagues insist that the new stem cells isolated differ from previously described human neural stem cells — the newly discovered stem cells are highly positive for both pericyte and mesenchymal stem cell markers and negative for hematopoietic, endothelial, microglial, and glial markers.

What does this mean?
• Pericyte stem cells are those that develop into the cells that are found in the central nervous system.
• Microglial and glial stem cells give rise to the glia, which are the supportive cells in the central nervous system that don’t conduct electrical charges like neurons.
• Hematopoietic stem cells are those that give rise to all blood cell types.
• Endothelial stem cells give rise to cells of the blood vessels and lymph nodes.

Plainly put, the stem cells can be developed more easily into the neurons and glia of the brain, and can potentially be used to replace damaged brain cells that are notorious for not being able to regenerate.

“Indeed, while the cells exhibited a mesenchymal phenotype and could be differentiated into osteoblasts (bone cells), chondrocytes (cartilage), and adipocytes (fat cells), they could also be epigenetically induced to differentiate along glial and neuronal lineages,” Dr. Brundin says. “This has not been reported for a human brain-derived progenitor cell before,” the team remarks.

In October, Dr. Brundin to became the first person to hold the Jay Van Andel Endowed Chair in Parkinson’s Research at the Van Andel Research Institute (VARI).

Plasticity and stability suggest potential
While the new stem cell’s specific function is still unclear, its plastic properties suggest great potential.

Found in embryos, as well as adults and children, stem cells are a type of cell that can renew themselves. They’re unspecialized and can take on the characteristics of other cells in the body. This is why they’re found in developing embryos — the stem cells there eventually generate all the cells of the entire body. In adults, they’re commonly found in bone marrow, where they replace other cells that have died or weakened because of aging or injury.

In recent years, scientists have discovered that adult stem cells can differentiate into various cell types — a phenomenon called stem cell transdifferentiation or plasticity: Neural stem cells from the brain can differentiate into ectoderm, mesoderm and endoderm. Stem cells from the bone marrow can differentiate into liver, lung, gastro-intestinal tract and skin.

Transdifferentiation can be induced by:
• Modifying the growth medium where stem cells are cultured in vitro or in a Petri dish in the lab.
• Transplanting them to an organ of the body different from the one they came from.

It’s cell plasticity that makes stem cells promising in the treatment of medical conditions involving damaged internal organs. Right now, thousands of researches are being undertaken across the world to find out if stem cells can be used to regenerate organ tissue. But for quite some time now, bone marrow stem cells have been routinely used in transfusions to treat blood-forming diseases like sickle cell anemia and leukemia.

Still, there’s no consensus among biologists on the prevalence and physiological and therapeutic relevance of stem cell plasticity.

Next steps: enhance the new stem cells
Writing in Plos One, the Lund investigators announce more encouraging findings that make the new stem cells a promising source of future brain disorder therapies:
• The new stem cells can be propagated efficiently over the long term as adherent cultures.
• The stem cells can be cloned.
• The stem cells retained a stable karyotype and full differentiation capacity even after being proliferated extensively.

The next step, the researchers say, is to try to control and enhance stem cell self-healing properties with the aim of carrying out targeted therapies to a specific area of the brain.

“Our findings show that the cell capacity is much larger than we originally thought, and that these cells are very versatile,” says Dr. Gesine Paul-Visse, Associate Professor of Neuroscience at Lund University and the study’s primary author.

“Most interesting is their ability to form neuronal cells, but they can also be developed for other cell types. The results contribute to better understanding of how brain cell plasticity works and opens up new opportunities to exploit these very features.”

“We hope that our findings may lead to a new and better understanding of the brain’s own repair mechanisms,” Dr. Paul-Visse adds. “Ultimately the goal is to strengthen these mechanisms and develop new treatments that can repair the diseased brain.”

That, in fact, is the focus of research at Lund’s Neuronal Survival Unit — its mission is to understand neurodegenerative diseases and develop new therapies that can benefit patients and caregivers.

Right now, the team is studying pathogenetic mechanisms and pharmacological treatment in cell and lab animals genetically modified to have Parkinson’s and Alzheimer’s. It’s also investigating stem cell replacement therapy with stem cells to repair damaged brains.

Established by Jay and Betty Van Andel in 1996, Van Andel Institute is an independent research organization dedicated to preserving, enhancing and expanding the frontiers of medical science.

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