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Spinal cord injuries: how could stem cells help?

Author Mary Views Posted at 2016/03/31

EuroStemCell (published on April 2, 2015)

The spinal cord transmits information between the brain and the rest of the body. Injury to the spinal cord, which currently affects some 333,000 Europeans, can cause paralysis, and there is currently no effective treatment. Could stem cells help?

Introducing the spinal cord
The spinal cord is the delicate tissue encased in and protected by the hard vertebrae of the spinal column. Together the brain and spinal cord form the body’s central nervous system.

The spinal cord is made up of millions of nerve cells that carry signals to and from the brain and out into other parts of the body. The information that allows us to sit, run, go to the toilet and breathe travels along the spinal cord.

How does the spinal cord work?
The main cell type found in the spinal cord, the neuron, conveys information up and down the spinal cord in the form of electrical signals. An axon (also known as a nerve fibre) is a long, slender projection of a neuron that conducts these signals away from the neuron's cell body. Each neuron has only one axon, and it can be as long as the entire spinal cord, up to 45cm in an adult human.

The axons that carry messages down the spinal cord (from the brain) are called motor axons. They control the muscles of internal organs (such as heart, stomach, intestines) and those of the legs and arms. They also help regulate blood pressure, body temperature, and the body’s response to stress.

The axons that travel up the cord (to the brain) carry sensory information from the skin, joints and muscles (touch, pain, temperature) and from internal organs (such as heart and lungs). These are the sensory axons.

Neurons in the spinal cord also need the support of other cell types. The oligodendrocyte, for example, forms structures that wrap around and insulate the axon. Called myelin, this insulating material helps the electrical impulse to flow quickly and efficiently down the axon.

What happens when the spinal cord is injured?
A spinal cord injury affects both neurons and the myelin sheath that insulates axons
Spinal cord injuries (SCI) are devastating and debilitating conditions affecting people all over the world, particularly young adults. They are associated with severe physical, psychological, social and economic burdens on patients and their families. To develop effective treatments for SCIs, a precise understanding of the main events following the injury and how these events interact is needed.

Spinal cord injuries generally involve two broad chronological phases that are sustained by the primary and secondary mechanisms of injury. Primary injuries include shearing, laceration, and acute stretching. Acceleration–deceleration events can also cause spinal cord injury, but very rarely lead to complete disruption of the spinal cord.

At a cellular level, axons are crushed and torn, and oligodendrocytes, the nerve cells that make up the insulating myelin sheath around axons, begin to die. Exposed axons degenerate, the connection between neurons is disrupted and the flow of information between the brain and the spinal cord is blocked.
The body cannot replace cells lost when the spinal cord is injured, and its function becomes impaired permanently. Patients may end up with severe movement and sensation disabilities. They will generally be paralyzed and without sensation from the level of the injury downwards. Injuries high in the neck, such as that suffered by Superman actor Christopher Reeve, paralyze the whole body including the arms and shoulders. A common level of injury is just below the ribs, resulting in normal arm function but paralyzed legs. Depending on the location and the extent of the injury patients may suffer complete or incomplete paralysis, and loss of feeling, sexual function and bowel control.

The severity of neurological injury, the level of the injury and the presence of a zone of partial cord preservation are accepted predictors of recovery and survival after SCI. The presence of spared axons crossing the injury site holds great therapeutic potential, and is the basis of a number of emerging therapeutic strategies.

How are spinal cord injuries treated now?
Despite the important advances in the understanding of spinal cord injuries, to date, almost all therapies that have shown promise at the preclinical stage of study have failed to translate into clinically effective treatments. Medical care immediately after the injury – including immobilising and bracing to stabilise the spine - can help to minimise the damage to nerve cells.  Rehabilitation can help patients regain physical and emotional independence.
How could stem cells contribute to spinal cord repair?
A spinal cord injury is complex, involving different kinds of damage to different types of cells. The environment of the spinal cord changes drastically during the first few weeks after injury (immune cells flow in, toxic substances are released, a scar is formed). A combination of therapies is needed, acting at the appropriate time-point and on the correct targets.

Studies in animals have shown that a transplantation of stem cells or stem-cell-derived cells may contribute to spinal cord repair by:

1. replacing the nerve cells that have died as a result of the injury;
2. generating new supporting cells that will re-form the insulating nerve sheath (myelin) and act as a bridge across the injury to stimulate re-growth of damaged axons;
3. protecting the cells at the injury site from further damage by releasing protective substances such as growth factors, and soaking up toxins such as free radicals, when introduced into the spinal cord shortly after injury.
4. Preventing spread of the injury by suppressing the damaging inflammation that can occur after injury

Different cell types, including stem cells, from a variety of sources, including brain tissue, the lining of the nasal cavity, tooth pulp, and embryonic stem cells, have been tested in these studies – mostly conducted in rat models of spinal cord injuries. None of these cells have produced more than a partial recovery of function, but it is an active area of research, and several different types of stem cell are being tested and modified.



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