A new study by scientists at the .NeuroRestore research center has identified the type of neuron that is activated and remodeled by spinal cord stimulation, allowing patients to stand up, walk and rebuild their muscles – thus improving their quality of life. This discovery, made in  nine patients, marks a fundamental, clinical breakthrough.

In a multi-year research program coordinated by the two directors of  .NeuroRestore – Grégoire Courtine, a neuroscience professor at EPFL, and  Jocelyne Bloch, a neurosurgeon at Lausanne University Hospital (CHUV) – patients who had been paralyzed by a spinal cord injury and who underwent  targeted epidural electrical stimulation of the area that controls leg movement  were able to regain some motor function.

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Northwestern University researchers have developed a new injectable therapy that harnesses “dancing molecules” to reverse paralysis and repair tissue after severe spinal cord injuries. In a new study, researchers administered a single injection to tissues surrounding the spinal cords of paralyzed mice. Just four weeks later, the animals regained the ability to walk.

By sending bioactive signals to trigger cells to repair and regenerate, the breakthrough therapy dramatically improved severely injured spinal cords in five key ways: The severed extensions of neurons, called axons, regenerated. Scar tissue, which can create a physical barrier to regeneration and repair, significantly diminished. Myelin, the insulating layer of axons that is important in transmitting electrical signals efficiently, reformed around cells. Functional blood vessels formed to deliver nutrients to cells at the injury site. More motor neurons survived.
After the therapy performs its function, the materials biodegrade into nutrients for the cells within 12 weeks and then completely disappear from the body without noticeable side effects. This is the first study in which researchers controlled the collective motion of molecules through changes in chemical structure to increase a therapeutic’s efficacy.

“Our research aims to find a therapy that can prevent individuals from becoming paralyzed after major trauma or disease,” said Northwestern’s Samuel I. Stupp, who led the study. “For decades, this has remained a major challenge for scientists because our body’s central nervous system, which includes the brain and spinal cord, does not have any significant capacity to repair itself after injury or after the onset of a degenerative disease. We are going straight to the FDA to start the process of getting this new therapy approved for use in human patients, who currently have very few treatment options.”

Stupp is Board of Trustees Professor of Materials Science and Engineering, Chemistry, Medicine and Biomedical Engineering at Northwestern, where he is founding director of the Simpson Querrey Institute for BioNanotechnology (SQI) and its affiliated research center, the Center for Regenerative Nanomedicine.

Source: https://news.northwestern.edu/

Intravenous injection of bone marrow derived stem cells (MSCs) in patients with spinal cord injuries led to significant improvement in motor functions, researchers from Yale University and Japan. For more than half of the patients, substantial improvements in key functions — such as ability to walk, or to use their hands — were observed within weeks of stem cell injection, the researchers report. No substantial side effects were reported.

The patients had sustained, non-penetrating spinal cord injuries, in many cases from falls or minor trauma, several weeks prior to implantation of the stem cells. Their symptoms involved loss of motor function and coordination, sensory loss, as well as bowel and bladder dysfunction. The stem cells were prepared from the patients’ own bone marrow, via a culture protocol that took a few weeks in a specialized cell processing center. The cells were injected intravenously in this series, with each patient serving as their own control. Results were not blinded and there were no placebo controls.

Yale scientists Jeffery D. Kocsis, professor of neurology, and Stephen G. Waxman, professor of neurology, neuroscience and pharmacology, were senior authors of the study, which was carried out with investigators at Sapporo Medical University in Japan. Key investigators of the Sapporo team, Osamu Honmou and Masanori Sasaki, both hold adjunct professor positions in neurology at Yale.

Kocsis and Waxman stress that additional studies will be needed to confirm the results of this preliminary, unblinded trial. They also stress that this could take years. Despite the challenges, they remain optimistic.

“Similar results with stem cells in patients with stroke increases our confidence that this approach may be clinically useful,” noted Kocsis. “This clinical study is the culmination of extensive preclinical laboratory work using MSCs between Yale and Sapporo colleagues over many years.”

“The idea that we may be able to restore function after injury to the brain and spinal cord using the patient’s own stem cells has intrigued us for years,” Waxman said. “Now we have a hint, in humans, that it may be possible.”

The findings are reported in the Journal of Clinical Neurology and Neurosurgery. 

Source: https://news.yale.edu/

Researchers at the University of California San Diego School of Medicine have successfully implanted grafts of neural stem cells straight into spinal cord injuries in mice and documented their functionality in mimicking the animals’ existing neuronal network after growing and filling the place of injury, a new study reports.

This stem cell breakthrough might be what patients who are living with spinal cord injury are waiting for. According to the press release, nearly 18,000 people in the U.S. suffer from spinal cord injury and 294,000 people live with it. Whether it is a permanent paralysis or diminished physical function, researchers were trying their hand at restoring these lost functions using stem cells lately. In order to solve this, the researchers used recent technology and were able to stimulate and record the activity of neuron populations with light rather than electricity, enabling them to see the connections.

They saw that graft neurons acted like the neural networks of the normal spinal cord even when there was an absence of direct stimulation. To further the research, the team stimulated regenerating exons from the mice’s brain and found that “some of the same spontaneously active clusters of graft neurons responded robustly.” This meant that these networks receive functional synaptic connections from inputs that typically cause movement, also being activated by light touch and pinches.

 “We knew that damaged host axons grew extensively into (injury sites), and that graft neurons, in turn, extended large numbers of axons into the spinal cord, but we had no idea what kind of activity was actually occurring inside the graft itself,” stated the study’s first author Steven Ceto.

What they didn’t know, however, was whether if host and graft axons were making functional connections.  “We showed that we could turn on spinal cord neurons below the injury site by stimulating graft axons extending into these areas. Putting all these results together, it turns out that neural stem cell grafts have a remarkable ability to self-assemble into spinal cord-like neural networks that functionally integrate with the host nervous system. After years of speculation and inference, we showed directly that each of the building blocks of a neuronal relay across spinal cord injury are in fact functional,” explained Ceto,

The team is now working to further enhance the functional connectivity of stem cell grafts and trying to move their stem cell graft approach into clinical trials. According to the researchers, a therapy might be achieved within a decade.

The study was published in Cell Stem Cell.

Source: https://www.cell.com/
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Source: https://news.rub.de/

Rutgers scientists have created a tiny, biodegradable scaffold to transplant stem cells and deliver drugs, which may help treat Alzheimer’s and Parkinson’s diseases, aging brain degeneration, spinal cord injuries and traumatic brain injuries. Stem cell transplantation, which shows promise as a treatment for central nervous system diseases, has been hampered by low cell survival rates, incomplete differentiation of cells and limited growth of neural connections.

So, Rutgers scientists designed bio-scaffolds that mimic natural tissue and got good results in test tubes and mice. These nano-size scaffolds hold promise for advanced stem cell transplantation and neural tissue engineering. Stem cell therapy leads to stem cells becoming neurons and can restore neural circuits.

“It’s been a major challenge to develop a reliable therapeutic method for treating central nervous system diseases and injuries,” said study senior author KiBum Lee, a professor in the Department of Chemistry and Chemical Biology at Rutgers University-New Brunswick. “Our enhanced stem cell transplantation approach is an innovative potential solution.”

The researchers, in cooperation with neuroscientists and clinicians, plan to test the nano-scaffolds in larger animals and eventually move to clinical trials for treating spinal cord injury. The scaffold-based technology also shows promise for regenerative medicine.

The study included researchers from Rutgers and Kyung Hee University in South Korea. The results have been published in  Nature Communications.

Source: https://www.eurekalert.org/