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.

A wheelchair skills camp for children with SCI

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By: Leanne Ramer and Bonita Sawatzky

A wheelchair skills camp for children with SCI

Mobility is an issue for most people with SCI, but one group of people that deserve special consideration is children with SCI who use wheelchairs. Depending on their age at the time of their injury, children and adolescents may need special support to gain confidence using a wheelchair. Currently no teaching is provided to children who get wheelchairs. ICORD researcher Bonnie Sawatzky recently investigated the effectiveness of a wheelchair skills training program for children, held in Vancouver.

Children from 7 to 19 years old with SCI participated in this pilot study. Participants performed a skills test in their manual wheelchair and answered questions about their normal activity levels. The children participated in a two-day wheelchair skills training camp, held on consecutive weekends, one week apart. In total, participants received 9 hours of wheelchair skills training. After the camp, the wheelchair skills test and the questionnaire were repeated. An additional questionnaire was administered 4 months later.

What was the most important finding?

Children with SCI performed better on the wheelchair skills test after the training camp. In addition, the responses to the questionnaire at 4 months after the camp suggested that the children experienced improvements in their independence and ability to perform tasks of daily living in the community.

What are some things we need to consider?

In this study, children with SCI demonstrated improvement in wheelchair skills under controlled testing conditions. More research is required to determine whether this improvement will translate into improved mobility in the community, and increased ability to participate in activities (e.g., in school).

What does this mean for people with SCI?

This study suggests that investing time in wheelchair skills training pays off. While this is probably true for everyone, few researchers have investigated the best way to accomplish wheelchair skills training in children with SCI. This study indicates that a short, intensive wheelchair skills camp can help children with SCI use their manual chair, which is likely to translate into increased participation in school, sports, and other activities. Thus we should encourage some formal training for children who use wheelchairs.

Restoring breathing after cervical SCI

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By: Andre Fallavollita

Recovery of breathing after SCI

Improving breathing function is a very high priority for treatment after SCI. People with high SCI often need ventilators to breathe, which is associated with unique challenges and health risks. Even patients who can breathe without a ventilator sometimes experience impaired breathing, which increases their risk of infections. In fact, the negative effects of impaired breathing are among the leading causes of death after SCI.

Restoring normal breathing after high SCI involves regrowing connections, across the injury site to the diaphragm. The diaphragm is crucial to breathing: it is the muscle that moves the majority of air in and out of the lungs. But there are two reasons that these connections are very difficult to regrow. First, the injured spinal cord is a very unfavorable location for growing nerves. Second, it is difficult to study a process that is so essential to life! However, scientists working in Cleveland, Ohio, recently demonstrated that they could succeed in regrowing injured nerves to a paralyzed diaphragm. Working in a rat model of cervical SCI, they combined a chemical treatment with a surgical graft: the chemical digested stop signals, to clear a path for growing nerves, while the graft made a bridge for the nerves, guiding them past the injury to reconnect with the diaphragm.

What was the most important finding?

Regrowth of nerves restored function to the paralyzed diaphragm. This recovery persisted for at least 6 months: in a rat, this represents a very significant time period, the equivalent of years to decades in humans.

What are some things we need to consider?

In order to succeed, the researchers had to combine chemical treatment with a complex surgery – the chemical alone had little benefit. Because the treatment is so complex, it will be challenging to move from laboratory experiments to clinical treatment.

What does this mean for people with SCI?

Although it is still experimental, this work demonstrates that we can bypass the site of SCI to restore breathing. Patients who presently need a ventilator may be able to regain the ability to breathe without it. Regaining the function of a single muscle could have a dramatic impact on the quality of peoples’ lives.

Original article: Alilain WJ, Horn KP, Hu H, Dick TE, Silver J. Functional regeneration of respiratory pathways after spinal cord injury. Nature. 2011 Jul 14;475(7355):196–200.

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.

 

 

Functional electrical stimulation cycling in women with SCI

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By: Nathan Santos 

 

What’s new in SCI Research?

People with spinal cord injury (SCI) often find that they lose bone mass. This leads to an increased chance of fractures, especially in the legs. Until now, treatment of this bone loss has been limited to the use of medication, but one area of interest lies in Functional Electrical Stimulation (FES) cycling. In FES cycling, electrodes are placed over the leg muscles used for cycling a bike. The participant mounts a stationary exercise bike, and a computer then stimulates the legs in a cycling pattern. ICORD researchers Andrei Krassioukov, Janice Eng and Darren Warburton wanted to measure how much FES cycling helps to improve bone quality. Women who had been living with SCI for more than a year, and who used wheelchairs for mobility, were recruited for participation. After training with FES cycles for six months, measurements showed improved bone density, and in addition, increased lean mass, meaning more muscle, and less fat, in the participants’ legs.

What was the most important finding?

FES cycling may increase muscle mass and bone mass in the legs, potentially reducing the risk of fracture among other benefits.

What are some things we need to consider?

This was the first study to link FES and bone quality in people with SCI, and it was completed on a very small scale. The next steps is a larger study, to confirm and expand the results. In this small study not all participants had the same results.

In addition, FES is expensive and time-consuming, so there may be practical concerns about whether it is suitable for everyone.

What does this mean for people with SCI?

Although more research does need to be done, FES may be a very promising possibility for improving muscle and bone mass in people with SCI.

Original article: Ashe MC, Eng JJ, Krassioukov AV, Warburton DER, Hung C, Tawashy A. Response to functional electrical stimulation cycling in women with spinal cord injuries using dual-energy X-ray absorptiometry and peripheral quantitative computed tomography: a case series. J Spinal Cord Med. 2010;33(1):68–72.

Sensory substitution for sexual rehab of men with chronic SCI

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 By: Nathan Santos

 

 

What’s new in SCI Research?

Sexual function is a significant issue for people with a spinal cord injury (SCI), and has been identified as a top priority by the community. ICORD researchers Jaimie Borisoff, Stacy Elliott and Gary Birch used a new technology to attempt to improve the sex lives of those with SCI. Participants in the study were sexually active adult males with SCI, some of whom were in long-term relationships.

The technology maps the stroking motion of a participant’s hand on the penis and synchronizes that motion to sensations on the tongue. This allows the participant to associate the motions on the tongue in a similar way to those occurring on the penis, via neuroplasticity or temporary sensory illusion. Participants trained with the device for several weeks and answered detailed sexual-health questionnaires.The results showed increased levels of sexual pleasure soon after training with the device.

What was the most important finding?

The most important finding in this study was the discovery that this type of technology and training can improve sexual pleasure. By associating the sensations felt on the tongue with the stroking of the penis, sexual rehabilitation techniques for those with SCI can be better understood and improved even further in the future.

What are some things we need to consider?

An important note is that the technology in this study did not improve feelings of orgasm. As the researchers had expected, none of the participants experienced an orgasm while undergoing training; this was a source of some real disappointment.

Also worth noting is the fact that although subjects reported improved feelings of sexual
sensation, they also experienced bouts of frustration throughout. These feelings, it is believed at least in part, may well have come from the increased expectations as each participant became more competent and successful with the equipment over time.

It is also worth noting that this first attempt at sexual neuroplasticity research in SCI leaves many unanswered questions with regards to optimal levels of training frequency and duration.

What does this mean for people with SCI?

This study demonstrates that those with SCI can experience improved feelings of sexual pleasure by undergoing sensory substitution training. This finding addresses one of the highest priorities for individuals living with SCI. There is no doubt that every step toward improved sexual feelings will be welcomed and well-received within the SCI community.

Original article: Borisoff JF, Elliott SL, Hocaloski S, Birch GE. The development of a sensory substitution system for the sexual rehabilitation of men with chronic spinal cord injury. J Sex Med. 2010 Nov;7(11):3647–58.

Epidural stimulation permits voluntary movement after complete SCI

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By: Leanne Ramer

What’s new in SCI Research?

A recent case study published in the Lancet1 has been receiving significant attention from the media.  In Louisville, Kentucky, a young man paralyzed from the chest down received intensive rehabilitation in combination with a surgical implant above his spinal cord. The implant is designed to deliver electrical stimulation to the spinal cord below the injury. It is specifically directed at the area controlling his legs, but overlaps with regions associated with control of bladder, bowel, and sexual function.

During rehabilitation sessions before receiving the implant, the young man relied upon the assistance of his therapists to stand and to step. For him to succeed previously, the therapists held his joints in place (Fig 1), supported his body-weight, and manually moved his legs through stepping motions.

Once the electrical stimulator was implanted and activated, the young man’s own arms were enough to move him from sitting to a standing position, and he was able to remain standing for minutes at a time without help, although stepping proved too difficult — sensationalistic headlines to the contrary.

What was the most important finding?

When the electrical stimulator was turned on, the young man could move his legs on command. While electrical stimulators have been used before in people with spinal cord injury, this is likely to be the best-documented instance of an individual regaining some voluntary movement after paralysis.

What are some things we need to consider?

As the authors remind us in the title, this is a case study: a report on one single individual with a unique spinal cord injury. Every injury is different, and we must wait to see whether this treatment works for other people. It is exciting and inspires much hope; however, like an early victory in a sports tournament there is much work still to be done.

It is also important to note that only leg muscles and movement were measured objectively. The subject also reported improved bladder, bowel, and sexual function after the implantation surgery, but there was no objective measurement of these improvements. Although they were of course extremely important to the individual, the assessment of their improvement was based only on his impression, and was not included as an objective finding.

What does this mean for people with SCI?

This means that even when no movement can be detected, some connections through the site of spinal cord injury may still exist. If we can find a way to provide amplification or “turn up the gain” for the nervous system, through electrical or other stimulation, we may be better able to harness those connections in the future. This study provides proof of this principle.

Figure 1: The subject stands with the help of his therapist 2

Original article: Harkema S, Gerasimenko Y, Hodes J, Burdick J, Angeli C, Chen Y, et al. Effect of epidural stimulation of the lumbosacral spinal cord on voluntary movement, standing, and assisted stepping after motor complete paraplegia: a case study. The Lancet. 2011 Jun;377:1938–47.