Functioning neural network grown from stem cells.

NEWS

For Immediate Release

July 13, 2005

LOS ANGELES -- Research published in the June edition of Neurosurgery, the official journal of the Congress of Neurological Surgions, documents how physicians in Stockholm, Sweden and Oslo, Norway collaborated with researchers at USC and Caltech to successfully produce functioning neurons from adult stem cells harvested from the ventricle area of a donor's brain.

The neurons were proven capable of communicating through synapses and holds promise that patients suffering from degenerative conditions such as Parkinson's disease, epilepsy and Huntington's chorea may one day be treated by growing enough neurons to replace cells destroyed by the disorders.

"We are able to develop a significant number of functional neurons that communicate in a network cells from very small biopsies," said Dr. Iver A. Langmoen, Professor of Neurosurgery at Karolinska Institute in Stockholm. "This creates a basis for study into how to harvest a few cells from the brain of a patient with a particular disease, cultivate healthy cells in the lab, and then transplant the normal cells back into the patient," he added.

The stem cells were obtained during a standard endoscopy procedure to treat hydrocephalus. The endoscope creates a small channel in the brain's ventricular wall to release excess cerebrospinal fluid.

The 2-4 millimeter tissue samples removed to create the channel were separated into single cells by placing them in an enzyme medium and subsequent passage through a strainer.

Each cell was then replicated within a culture of growth factor to form a small sphere of cells known as a neurosphere. A typical neurosphere consists of about 300 immature cells.

Individual neurospheres were then separated into their component cells and the replication process, or passage, was repeated. Four passages have the potential to yield about 2.5 million cells from a single originating cell.

The young cells at that point have not yet developed into functional brain tissue. They are placed in a new environment to stop the replication process and to stimulate their development into a specific type of brain cell.

Researchers believe manipulating the combination of proteins in the culture activates an internal mechanism determing the type of brain tissue the cell becomes.

It takes about four weeks for a stem cell to become a mature neuron. Some of the cells were stained with neuronal antibodies that indicated they were neurons. The test was encouraging, but it did not prove the researchers had grown functioning neurons.

The most valid test to verify the neurons functioned was to observe whether they exhibited characteristic firing patterns occurring naturally in the brain.

Individual cells in the cultures responded to glutamate, which is the most common chemical in the brain for stimulating neurons. Most importantly, when a single cell was activated, adjacent cells produced an electrical response characteristic in both pattern and time interval for synaptic transmission. Cellular communication had taken place.

The manifold implications of this landmark study for the future treatment of neural diseases and trauma make it among the most significant advances in neuroscience. It's equally meaningful for the advancement of stem cell research and gives credence to the concept of autotransplantation in which a patient's own cells may provide a cure without concern for adverse immune response that is a factor in all current transplantation procedures.

Ongoing collaborative work with Drs. Charles Liu at USC and David Tirrell of Caltech will study how artificial protein matrices outside the cell direct the behavior of Dr. Langmoen's neural networks.

"Dr. Langmoen's work is very exciting, because now we have direct evidence of synaptic transmission between neurons grown from stem cells," Dr. Liu said.

Neurosurgery, the Official Journal of the Congress of Neurological Surgeons is the most complete publication about the contemporary field of neurosurgery. Members of the Congress and non-member subscribers receive 4,000 pages per year of the latest science, technology, medicine and full-text online access to the world's most recent neurosurgery information. Neurosurgery's editorial office is located in Los Angeles, CA and is published by Lippincott Williams & Wilkins of Philadelphia, PA.

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