Stem Cell in Florida: UCF Team Finds Hope in Umbilical Stem Cell Cords

U.S. scientists grow nerve cells from umbilical stem cells: What could be more tragic than a woman in her prime, trapped in a chronic, unpredictable and progressive disease of the central nervous system that causes her to suffer from constant pain, spasms and tremors, incontinence, constipation, memory loss, difficulty concentrating, anxiety, depression—and eventually, paralysis and blindness?

Or a young man suddenly and fully paralyzed by a spinal cord injury from a violent attack or accident?

Severe crippling and lifelong incapacitation — that’s what it means to suffer from multiple sclerosis (MS) or a spinal cord injury (SCI).

In MS, the immune system attacks and destroys the insulation of nerves and, over time, the nerves themselves. As more and more nerves get affected, people with MS lose more of the functions controlled by the nervous system—speech, memory, vision, movement.

MS sufferers have roughly the same life expectancy as healthy people, but for about 400,000 people in the United States and more than two million worldwide who suffer from the dreaded disease, life becomes unbearable and they end up taking their own lives.

Meanwhile, around 230,000 people in the U.S. and about two million worldwide live with a spinal cord injury caused by a single violent attack or a car accident. In the U.S., about 11,000 new injuries occur each year.

For people with spinal cord injuries, life is a struggle to endure paralysis—of both legs, or full paralysis of limbs and torso.

Currently, there are no cures for both conditions — only therapies to slow the course of MS or ease the hardships experienced by people with SCIs.

First step toward cure
But new findings from the University of Central Florida (UCF), published in the Jan. 18 issue of the journal ACS Chemical Neuroscience, comprise a vital step toward finding a cure for the two dreaded nervous system ailments.

The team of researchers under UCF bioengineer Dr. James Hickman were able to successfully grow oligodendrocytes—or the critical structural cells that insulate nerves in the brain and spinal cord–from human multipotent progenitor cells (MLPCs) derived from umbilical cord blood.

This achievement is a breakthrough in at least three fronts.

First is the medical potential of growing oligodendrocytes. Injected into the body at the point of a spinal cord injury, oligodendrocytes may be able to promote repair.

The team’s achievement may also lead to the development of treatments for multiple sclerosis and similar conditions, since oligodendrocytes produce the myelin that insulate nerve cells—the very thing being attacked by the immune system of those who suffer MS.

Loss of myelin leads to MS and other related conditions such as diabetic neuropathy—and the injection of new, healthy oligodendrocytes might regenerate damaged myelin. This may make it possible for nerve cells to begin to conduct again the electrical signals that guide movement and other functions, thus improving the condition of people suffering from MS and similar diseases.

While the production of oligodendrocytes from cord blood stem cells is only a first step to potential medical treatments, it is a crucial first step, and Dr. Hickman’s team hopes to pursue both options.

“Multiple sclerosis is one of the holy grails for this kind of research,” said Dr. Hickman, leader of the research group. His team is collaborating with Stephen Lambert at UCF’s medical school, also one of the authors of the paper.

A first: mature cells from cord stem cells
On another front, the UCF team’s feat is also a breakthrough in the overall development of stem cell therapies because it’s the very first time that stem cells from umbilical cords have been converted into other types of cells.

“This is the first time this has been done with non-embryonic stem cells,” says Dr. Hickman. “We’re very excited about where this could lead because it overcomes many of the obstacles present with embryonic stem cells.”

Unlike human embryonic stem cells (hESCs), stem cells derived from umbilical cords are not surrounded by controversy and ethical dilemmas because they are taken from a source that is generally thrown away.

After a baby is born and the umbilical cord is cut, some blood remains in the blood vessels of the placenta and the portion of the umbilical cord that remains attached to it. This blood, called “cord blood,” is no longer needed by the baby.

In recent years, this cord blood has been harvested, with the permission of birth mothers, to produce stem cells and other cord-blood products like various types of progenitor cells.

The human multipotent progenitor cells (MLPCs) derived by Dr. Hickman’s team comes from umbilical cord blood.

Meanwhile, the controversy surrounding the use of embryonic stem cells has hampered the search for stem cell treatments.

Mark Schrope, writing for the UCF Today, reports that Geron, Menlo Park, California-based pharmaceutical company had developed a treatment for spinal cord repair based on embryonic stem cells, but the ethical and public concerns tied to human embryonic stem cell research pushed the U.S. Food and Drug Authority to drag out its approval over a period of 18 months. This led the company to shut down its embryonic stem cell division—underscoring the need for other alternatives to hESCs.

This, in fact, was the main aim of Dr. Hickman’s team, when it embarked on its research.

“There is a crucial need to establish alternatives to hESC as a source of stem cells for clinical applications,” the researchers write in the ACS Chemical Neuroscience journal.

“This is especially true for applications to disease and injury in the central nervous system (CNS), as recent clinical trials have been delayed by the Federal Drug Administration for hESC but have been relatively straightforward for adult stem cells and stem cells from other sources,” they write.

Aside from the fact that the UCF researchers have found a way forward for stem cell research, circumventing the controversies surrounding embryonic stem cells, there is a third reason why their work is a breakthrough.

Umbilical cells generally have not been found to cause immune reactions, unlike hESCs, and this boosts their potential use in medical treatments.

The team is also plans to develop the techniques fully to grow oligodendrocytes in the lab—and by doing so build a “model system” lab development of oligodendrocytes. Such a system can be used to study the loss and restoration of myelin better as well as to test potential new treatments.

“We want to do both,” Dr. Hickman said. “We want to use a model system to understand what’s going on and also to look for possible therapies to repair some of the damage, and we think there is great potential in both directions.”

Environment and chemical triggers
When the researchers set out to transform umbilical stem cells into oligodendrocytes, the main challenge they faced was deciphering the chemical and other triggers that will encourage the stem cells to transform into a desired cell type.

To start, Hedvika Davis, a postdoctoral researcher in Hickman’s lab, and the paper’s lead author, looked for clues from past research.

Previous studies found components in oligodendrocytes that bind with the hormone norephinephrine. To Davis, this suggested that the cells normally interact with this norephinephrine—and this chemical may be one of the triggers that stimulate the growth of oligodendrocytes.

Starting out with this, the team tested norephinephrine. They were right: they found that the chemical, together with other stem cell growth promoters, caused the umbilical stem cells to differentiate—or change—into oligodendrocytes.

But the conversion only went so far: the transformation stopped short of reaching a level similar to what’s found in the human nervous system.

The team decided that, aside from simulating neurochemistry, they might also need to simulate the physical environment of nerve cells.

Aiming to approximate the physical restrictions that cells face in the body more closely, the team set up a more confined, three-dimensional environment: they grew the stem cells on top of a microscope slide—but with a glass slide above them. It was only after making this change, on top of still providing the cells with norephinphrine and other chemicals, that the cells began to fully mature into oligodendrocytes.

“We realized that the stem cells are very sensitive to environmental conditions,” Davis said.

Besides Hickman and Davis, the other authors of the paper are Xiufang Guo, Stephen Lambert, and Maria Stancescu, all from the University of Central Florida.

Another first: ‘human-on-a-chip’ first step
Dr. Hickman’s bioengineering team is no stranger to pioneering developments in stem cell research.

Last November (2011), a team of University of Central Florida researchers under Dr. Hickman was responsible for another first: they were able to use stem cells to grow neuromuscular junctions between human muscle cells and human spinal cord cells. These junctions are the key connectors the brain uses to communicate and control muscles in the body.

That feat is a vital step in developing “human-on-a-chip” systems—or models that recreate how organs or a series of organ functions in the body.

Before they are tested on humans, drugs could be tested first on the human cells in these “human-on-a-chip” systems—made up of various miniature organs connected realistically to simulate human body function. The results of such tests would be closer to the results derived from real use of the drugs. Testing on these systems may also prove to be more effective than testing on mice.

Using such systems of models could accelerate medical research and drug testing, delivering life-saving breakthroughs much more quickly than the typical 10 years it now takes to for medications to be tested in animal and patient trials.

“These types of systems have to be developed if you ever want to get to a human-on-a-chip that recreates human function,” said Dr. Hickman. “It’s taken many trials over a number of years to get this to occur using human derived stem cells.”

Apart from being a key component for any “human-on-a-chip” model, the nerve-muscle junctions may also help in the development of treatments for ailments of the nerve-muscle junctions, such as amyotrophic lateral sclerosis (ALS) or Lou Gehrig’s disease, spinal cord injury and in other debilitating or life threatening conditions.

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