Research using spinal cord-injured mice suggests that human embryonic stem cells transplanted into mouse spinal cord may be able to differentiate into specific cells that produce GABA neurons that may help alleviate SCI-related side effects.
These side effects include neurogenic bladder dysfunction and central neuropathic pain.
GABA (gamma-Aminobutyric acid) is an inhibitory neurotransmitter that is found throughout the central nervous system. It plays an important role in reducing the excitability of neurons by binding to receptors that act on synapses, explains a media release from Cell Press.
“We reasoned if we could take inhibitory neurons and directly place them into the spinal cord in the regions that are overactive, they might integrate into those circuits and suppress the activity,” says senior author Arnold Kriegstein, director of the Developmental and Stem Cell Biology Program at the University of California, San Francisco (UCSF).
In the study, published recently in Cell Stem Cell, Kriegstein and collaborator Linda Noble-Haeusslein, a professor in the Departments of Neurological Surgery and Physical Therapy and Rehabilitation Science at UCSF, used GABAergic inhibitory neuron precursors called MGE-like cells that were derived from human embryonic stem cells.
The neural precursor cells were placed into the spinal cords of mice 2 weeks after injury had been induced, where they could differentiate into GABA-producing neuron subtypes and form synaptic connections, the release notes.
“Rather than implanting these cells into the site of injury, at the mid-thoracic level, we injected them in the lumbosacral region, where the circuits are known to be overactive,” says Thomas Fandel, a research specialist at UCSF and the study’s co-first author, in the release. “Six months later we could see broad dispersion of the cells in that area. They were integrated into the spinal cord.”
The researchers used several measures to determine whether the stem cells were effective in alleviating neuropathic pain and bladder dysfunction at 6 months. To assess for bladder control, the mice were placed in cages with filter paper that showed where the mice had urinated. The treated mice had fewer, larger spots, indicating less leakage. Bladder function was also assessed by measuring bladder volume and tension, which confirmed the improved voiding ability of animals receiving transplants.
By 6 months after transplant, animals exhibited significantly reduced pain sensitivities. Grooming and scratching behaviors were also evaluated, as decreased GABA in the spinal cord can similarly cause pathological itch (pruritus). The researchers found that mice receiving the stem cell transplants showed decreased overgrooming compared to controls, the release explains.
“The fact that these cells were implanted in the spinal cords 2 weeks after injury is also important to note,” says Alpa Trivedi, a researcher at UCSF and co-first author of the study, according to the release. “Many of the current Phase I trials for spinal cord injury are run in the acute phase, which is right after injury. But the vast majority of people with spinal cord injuries are the chronic patient population, and a treatment that might work for them would capture a larger number of patients who are really in need of better treatments.”
“The current approaches for treatment are not very effective and clearly more options are needed,” Fandel states in the release. “Our hope is that this treatment would last a long time, or maybe even be permanent.”
[Source(s): Cell Press, Science Daily]