) in the spinal cord. Using human embryonic stem
cells capable of differentiating into medial ganglionic eminence (MGE)-like
cells, which produce GABA, may help reduce the severe disability caused chronic
pain and bladder dysfunction in such patients.
‘Stem cell treatment offers new hope for chronic pain relief in spinal cord injury patients.’
The investigators of this study employed precursors of GABAergic
inhibitory neuron called MGE-like cells derived from human embryonic stem cells
This study involved a joint effort between senior authors Arnold
Kriegstein, Director of the Developmental and Stem Cell Biology Program at the
University of California, San Francisco (UCSF), and Linda Noble-Haeusslein, a
professor in the Departments of Neurological Surgery and Physical Therapy and
Rehabilitation Science at UCSF. It addressed the issues of neuropathic pain and
bladder dysfunction, both of which are at least partly attributed to overactive spinal cord circuits.
"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 Kriegstein.
Details Of The Study
The GABAergic neural precursor cells (MGE-like cells) were placed within
the spinal cords of mice two weeks after inducing spinal injury, where they
could differentiate into GABA-producing neurons and form synaptic connections.
"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. "Six months later we could see broad
dispersion of the cells in that area. They were integrated into the spinal
Testing The Efficacy Of
Human Stem Cells In Mice
The researchers employed several methods to find out whether the stem
cells were effective in alleviating neuropathic
and bladder dysfunction at six months. To test
for bladder control, the mice were placed in cages with filter paper to
indicate where the mice had urinated. The transplanted mice had lesser, and
bigger spots, indicating less leakage. Bladder function was also assessed by
estimating bladder volume and tension, which validated the better voiding
ability of animals receiving transplants.
Six months after transplant, animals exhibited markedly reduced pain
sensitivities. Grooming and scratching behaviors were also evaluated, as
decreased GABA in the spinal cord can also lead to a pathological itch
(pruritus). The investigators found that mice receiving the stem cell
transplants showed a reduced overgrooming compared to controls.
"The fact that these cells were implanted in the spinal cords two weeks
after injury is also important to note," says Alpa Trivedi, a researcher at
UCSF and co-first author of the study. "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."
About Spinal Injuries
cord injuries result from a sudden impact to the spine that may result in
crushing or compression of the vertebrae.
injuries are usually characterized by paralysis
and loss of sensation
or numbness below the level of injury. The extent of
injury determines the degree of paralysis and numbness.
- Occurrence of a chronic neuropathic
pain related to nerve injury and damage,
- Loss of bladder
and bowel control
- Increased vulnerability to respiratory
is managed with pain medications such as opioid
analgesics, and certain antidepressants
. These are only partially effective and may cause many
side effects. Bladder dysfunction is managed with anticholinergics, and may
lead to dry mouth or dizziness. Botulinum toxin
has been tried to overcome
bladder spasms, but not found to be very effective.
quality of life for spinal injury patients thus remains challenging, even with
Scope Of This Study In
more research needs to be done, the employment of human stem cells instead of
mouse stem cells in their study is a step forward.
and bladder dysfunction remain significant quality-of-life issues for many people with spinal cord injuries. Inhibitory
cell-based neuro-therapy is a new approach and has shown promise to date in
early animal studies, warranting further development," says Cory Nicholas, a
conclusion, the researchers hope that their work would result in a longer
lasting or even a permanent solution to spinal injury patients, especially since
the presently available modalities
of treatment are not very satisfactory.
- NINDS Spinal Cord Injury Information Page
- Spinal cord injury - (http://www.mayoclinic.org/diseases-conditions/spinal-cord-injury/basics/symptoms/con-20023837)