How to Repair Injured Spinal Cord Using Patients’ Own Stem Cells

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/

How To Implant Neural Stem Cell Grafts To Cure Spinal Cord Injuries

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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Early-Stage Detection Of Alzheimer’s In The Blood

Two major studies with promising antibodies have recently failed – possibly because they have been administered too late. A new very early-detection test gives rise to hope. Using current techniques, Alzheimer’s disease, the most frequent cause of dementia, can only be detected once the typical plaques have formed in the brain. At this point, therapy seems no longer possible. However, the first changes caused by Alzheimer’s take place on the protein level up to 20 years sooner. A two-tier method developed at Ruhr-Universität Bochum (RUB) can help detect the disease at a much earlier stage. The researchers from Bochum published their report in the March 2019 edition of the journal “Alzheimer’s and Dementia: Diagnosis, Assessment and Disease Monitoring”.

This has paved the way for early-stage therapy approaches, where the as yet inefficient drugs on which we had pinned our hopes may prove effective,” says Professor Klaus Gerwert from the Department of Biophysics at RUB.

In Alzheimer’s patients, the amyloid beta protein folds incorrectly due to pathological changes long before the first symptoms occur. A team of researchers headed by Klaus Gerwert successfully diagnosed this misfolding using a simple blood test; as a result, the disease can be detected approximately eight years before the first clinical symptoms occur. The test wasn’t suitable for clinical applications however: it did detect 71 per cent of Alzheimer’s cases in symptomless stages, but at the same time provided false positive diagnoses for nine per cent of the study participants. In order to increase the number of correctly identified Alzheimer’s cases and to reduce the number of false positive diagnoses, the researchers poured a lot of time and effort into optimising the test.

As a result, they have now introduced the two-tier diagnostic method. To this end, they use the original blood test to identify high-risk individuals. Subsequently, they add a dementia-specific biomarker, namely tau protein, to run further tests with those test participants whose Alzheimer’s diagnosis was positive in the first step. If both biomarkers show a positive result, there is a high likelihood of Alzheimer’s disease. “Through the combination of both analyses, 87 of 100 Alzheimer’s patients were correctly identified in our study,” summarises Klaus Gerwert. “And we reduced the number of false positive diagnoses in healthy subjects to 3 of 100. The second analysis is carried out in cerebrospinal fluid that is extracted from the spinal cord.

Now, new clinical studies with test participants in very early stages of the disease can be launched,” points out Gerwert. He is hoping that the existing therapeutic antibodies will still have an effect. “Recently, two major promising studies have failed, especially Crenezumab and Aducanumab – not least because it had probably already been too late by the time therapy was taken up. The new test opens up a new therapy window.”

Source: https://news.rub.de/

Stem Cell Therapy Could Treat Alzheimer’s And Parkinson’s

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 injuriesStem 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/