Researchers at Karolinska Institutet have shown how the transplantation of stem cells improves recovery from spinal injury. However, a painful condition can also develop, which can be prevented if the stem cells are supplemented with a certain gene that controls their maturing process. The results are important for planning of stem cell therapy trials on patients with spinal injury.
Spinal injury confines some 150 Swedes a year to wheelchairs. The damage cause the loss of movement and sensation below the level of injury. A research team at Karolinska Institutet has now shown using rat models that the introduction of stem cells following such injury is effective, although a double-edged sword: while on the one hand the injection of stem cells into the damaged area of the spine improves motor function (movement) inferior to the injury level, scientists found that the rats developed greater pain sensitivity just superior of it.
In a follow-up study, a special gene, neurogenin-2, was added to the stem cells while they were developing in culture. When stem cells containing this gene were transplanted into the damaged spinal cord, the adverse pain effects failed to appear while the enhancement of motor function improved. Sensory function (feeling) below the injury also clearly improved.
The aggravated sensitivity to pain was thought to be the result of the fact that many stem cells developed into astrocytes, a kind of glial cell that encourages the growth of pain axons in the spinal cord by secreting substances that stimulate neuronal development.
The researchers found that the presence of neurogenin-2, a “transcription factor” that regulates the activity of other genes during the stem cell maturing process, inhibited the development of astrocytes and encouraged the formation of oligodendrocytes, another type of glial cell that forms the fatty myelin sheaths around the axons. The small number of astrocytes that developed from the neurogenin-2-bearing stem cells corresponded to the lack of growth of pain axons. The greater number of oligodendrocytes that were produced by the neurogenin-2-bearing stem cells also corresponded to a greater volume of white substance, i.e. myelin coated nerve fibres, in the damaged area.
With the help of functional Magnetic Resonance Imaging (fMRI), the team, working from KI’s experimental MRI centre, has managed for the first time to demonstrate the return of sensory function following spinal injury. An advantage of the fMRI technique is that it can be used to compare results from animal and human studies if and when new therapies for the treatment of spinal injury can be tested on patients.
Allodynia limits the usefulness of intraspinal neural stem cell grafts and directed differentiation improves outcome
Christoph Hofstetter, Niklas Holmström, Johan Lilja, Petra Schweinhardt, Jinxia Hao, Christian Spenger, Zsuzsanna Wiesenfeld-Hallin, Shekar Kurpad, Jonas Frisén, Lars Olson
Nature Neuroscience Online February 13, 2005
In print: Nature Neuroscience March 2005
For more information, please contact:
Professor Lars Olson, Department of Neuroscience, Karolinska Institutet,
phone +46 8 524 870 50, +46 70 670 3388 or mail [email protected]