Category Archives: biology

Stem cells and SCI: Unrestricted somatic stem cells

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By: Kevin Chi

What’s new in SCI Research?

Stem cell therapy is a potential treatment strategy for spinal cord injury (SCI), as well as other neurological disorders. However, there is no agreement about the best source or type of stem cells for treatment of SCI.

In this study, published in Brain, the researchers used an animal model of acute SCI and transplanted only “unrestricted somatic stem cells” (USSCs). These are a type of stem cell retrieved from human umbilical cord blood, discovered by German researchers in 2004. These cells are pluripotent, meaning they can become nearly any type of cell, including nerve, bone, cartilage, liver, heart, or blood cells. After transplantation of USSCs into animals with acute SCI, the researchers noticed some very interesting results.

What was the most important finding?

The researchers first showed that the USSC treatment promotes regrowth of axons — the connecting arms of nerve cells. They also showed that injured animals with the USSC treatment had smaller amounts of tissue damage.

In general, it is also important to look at functional outcomes, since smaller lesion sizes and regrowth of axons do not always translate into improvements in function. The axons must demonstrate sufficient regrowth and reconnection to result in actual improvements such as improved motor functions. In this study, the researchers examined several different functional outcomes in their animal model, all of which evaluated different aspects of locomotion: stepping, hindlimb movements, coordination of forelimbs and hindlimb, and paw placement. The results therefore showed that treatment with USSCs resulted in improved motor function.

What are some things we need to consider?

How do stem cell therapies actually result in functional improvements? It is often assumed that the healing effects of stem cells are a result of the cells specializing into cells that replace the tissue damaged in SCI. Interestingly, this study suggested that this assumption might not be true. Instead, the researchers found that there may be different mechanisms that explain the findings: they showed evidence that the USSCs release substances that may promote axon growth. Understanding exactly how stem cells accomplish their beneficial effects will do a great deal to optimize their use as treatments.

We must also take into consideration that this study was carried out in an animal model. Although this study does show promising results in the model, we must always be cautious in translating this to a human population. Many animal studies have shown promising treatments for SCI, but these results do not always translate into useful therapies for humans.

What does this mean for people with SCI?

Given the results seen in this animal model, USSCs may be a suitable stem cell source to provide clinical applications for people with SCI.

Original article: Schira, J., Gasis, M., Estrada, V., Hendricks, M., Schmitz, C., Trapp, T., Kruse, F., Kögler, G., Wernet, P. and Müller, H.W. (2011) Significant clinical, neuropathological and behavioural recovery from acute spinal cord trauma by transplantation of a well-defined somatic stem cell from human umbilical cord blood. Brain 135; 431-446.

Regrowth of nerves in the adult spinal cord

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By: Ivan Chiu

What’s new in SCI Research?

There are generally two ways that nerves can reconnect after SCI. First, the injured nerves can regrow to restore the lost connections; this is known as regeneration. Second, undamaged nerves surrounding the injury can branch out and form new circuits to replace lost connections, which is referred to as plasticity or sprouting. Both processes have the potential to restore function after SCI.

One of the most important circuits in humans consists of nerves controlling voluntary movement, including fine movement of the hands. This is called the corticospinal system — achieving new growth in corticospinal nerves is one of the biggest goals of SCI research. They are some of the most important nerves, but are difficult to work with, because nerves in the brain and spinal cord are inherently reluctant to grow.

An important study in Nature Neuroscience suggests that success in corticospinal regrowth might be increasing. The researchers conducted experiments in animal models of SCI to examine the role in nerve growth of a protein named mTOR. They found that mTOR regulates nerve growth: mTOR is activated in nerves that are growing and deactivated in nerves that have stopped growing — including corticospinal nerves in the adult.

Obviously the researchers are working to reactivate the mTOR protein, but it is present in many parts of the body, and has many functions, so it is very important to restrict the effect just to the corticospinal nerves. To do this, these scientists have developed a genetic trick to activate mTOR only in corticospinal nerves.

What was the most important finding?

When mTOR was activated, corticospinal nerves showed growth of uninjured nerves, and regeneration of nerves that had been injured by cervical SCI. Some new nerves formed new connections below the site of the injury.

What are some things we need to consider?

This was a genetic study performed in an animal model. More research will need to be done — including clinical trials in people with SCI – before these findings can be translated to clinical use.

What does this mean for people with SCI?

This study is the most dramatic demonstration yet published of regeneration in the injured spinal cord. It shows that regrowth of damaged nerves can occur through the site of an injury, and that SCI researchers are making progress in achieving true regeneration.

Original article: Liu K, Lu Y, Lee JK, Samara R, Willenberg R, Sears-Kraxberger I, et al. PTEN deletion enhances the regenerative ability of adult corticospinal neurons. Nature neuroscience. 2010;13(9):1075–81.