Neuroscientist Pengzhe (Paul) Lu has broken through a major set of obstacles facing SCI cure research. After years of painstaking work at the University of California, San Diego, Lu has largely reversed complete sub-acute SCI in rats with a combination of growth factors and neural stem cells embedded in a grafting gel. This is believed to be the first time in history that science has found a way to restore anything like this level of function in mammals with completely severed cords.
“This opens the door,” Lu says, referring specifically to indicators that the new processes should also work well in humans. His findings were published in the Sep. 14 issue of the scientific journal, Cell.
Lu’s approach is producing 200 times as many axons growing into the natural nervous tissue as previously achieved by any neuroscientist, according to Mark Tuszynski, of UCSD’s Department of Neurosciences’ Center for Neural Repair, and the study’s director. Axonal growth lengths are also 10 times longer than in the past, with “significant functional improvement” in the test animals.
Recovery of motor function remains weak, however, and with poor coordination.
“We do see a functional improvement,” Lu says. “It’s good, but it’s still not good enough,” he cautions — adding that the treated rats could not bear weight on their hind legs. He’s hard at work on a solution to this problem.
It took six years of work just to develop the growth factor cocktail that produces this robust stem cell survival rate in the grafts. Other studies have produced some tantalizing levels of stem cell survival and even significant axonal growth, but these grafted stem cells are not merely surviving in small percentages — they are thriving, re-crafting their surroundings and reaching out to re-connect motor pathways effectively enough to produce full mobility at all joints in the animals’ hind legs.
Lu characterized the results as “amazing” — a word used very sparingly by researchers and rightly held in great suspicion by those with SCI. But Lu is a 15-year T10-11 complete para himself (following an auto accident) — and he believes this is a significant breakthrough.
Remarkably, this degree of cord restoration can be accomplished not only with rat neural stem cells, but with human neural stem cells grafted into rats — a feat that some considered nearly impossible when Lu first proposed taking this approach. Some might wonder what the point of this bit of biological acrobatics could be, but the implications are profound: If human and rat stem cells are interchangeable in this way, it implies that the whole process is likely to work in humans. This, of course, remains to be proven.
Lu reports that, structurally, the stem cell graft is “almost like a reconstituted spinal cord.” No added growth factors below or above the graft site were needed to produce the connectivity seen in the study animals, but it is hoped that this additional trick will produce even better results in future testing. The width of the injuries overcome is also quite impressive, with the graft occupying two-thirds of a spinal cord level.
And there was another jaw-dropper of a result from this study: Lu’s neural stem cells remodeled and passed through collagen scarring. Many neuroscientists have long expected that this type of thick scar tissue would stop axons cold without some separate major scientific breakthrough. Not so.
“The stem cell is so great, the stem cell can modify the scar tissue,” Lu says.
It’s a result he didn’t even hope for when he began the study. He’s not even sure how the remodeling was done, but it’s very clear under the microscope that remodeling occurred, and occurred with smooth natural transitions. This means that a cure of SCI caused by complex penetrating injuries may keep pace with a cure for the more common bruised-cord injuries, rather than lagging behind by years or decades.
“This verifies the great potential of stem cells,” Lu says. “We still need some real function,” he cautions, before human trials can be justified. But Lu hopes that with about three years and $3 million, funded by a California Institute for Regenerative Medicine grant, UCSD will be able to reach that goal.
You can read more about UCSD’s SCI cure research by visiting them on the web at: http://tuszynskilab.ucsd.edu/sci.php.
Life in Action Contributor