Stem cell-filled implant restores some spinal cord …

By Dr. Matthew Watson

Stem cell-filled implants helped repair spinal cord damage in animals, according to a study led by UC San Diego scientists. If all goes well, the implants with neural stem cells could be ready for testing in human patients in a few years.

Rats with completely severed spinal cords regained some voluntary motion after getting the implants, said the study, published Monday in the journal Nature Medicine. The study is online at j.mp/ucsdspine.

They were able to move the joints of their lower legs, said study co-author Dr. Mark Tuszynski. They couldn't support their weight very well, but they could move the legs around the joints. If one were to project what this means to humans, it might mean that the legs are still weak, but that with an assist they would be able to control them.

The next step is to repeat the procedure in monkeys, said Tuszynski, director of the Translational Neuroscience Institute at UC San Diego School of Medicine.

If successful, it would fulfill one of the biggest hopes for stem cell therapy.

Repairing spinal cord injuries has long been a major goal of the states stem cell program, the California Institute for Regenerative Medicine, or CIRM. The agency was formed in 2004 with the passage of Prop. 71. The late actor Christopher Reeve figured prominently in the campaign for Prop. 71.

While there have been encouraging reports of individual spinal cord injury patients benefiting from stem cell-based therapy, no such treatment has been approved as safe and effective. So scientists at UCSD and elsewhere are trying to make a treatment that can be reliably replicated.

Another study with neural stem cells without the implant has shown benefit in monkeys after spinal cord injury, Tuszynski said. This work is closer to the clinical stage.

The rat implants were constructed by 3D bioprinting of a biologically compatible hydrogel, which is mostly made up of water. These 2-millimeter-wide implants contain tiny channels that guide growth of neural stem cells, also called neural progenitor cells. The cells matured into neurons and reconnected severed nerves, Tuszynski said.

Besides guiding growth, the implants allowed blood vessels to grow, nourishing the newly formed cells. This process, called vascularization, has been hard to achieve in growing new tissue. But with the biologically compatible implants, vascularization occurred spontaneously.

The implants also protected the neural stem cells from the inflammatory damage associated with a fresh injury.

This is a nice marriage of the technology of bioengineering and 3D printing with stem cell biology to treat a really important human disease that needs better therapy, Tuszynski said.

Implants can be quickly custom-made for human spinal cord injuries, according to the study. Researchers bioprinted implants of 4 centimeters within 10 minutes. These were made according to MRI scans of real human spinal cord injuries.

Two other UCSD study authors, Shaochen Chen and Wei Zhu, have co-founded a San Diego startup, Allegro 3D, to commercialize the rapid bioprinting technology. Allegro is doing this independently of the spinal cord injury research.

We will be talking to people to find a partner, said Chen, a founding co-director of the Biomaterials and Tissue Engineering Center at UC San Diego. It takes money, time and effort, so it won't be done in a university setting.

The neural stem cells are produced from a lineage of human embryonic stem cells. This lineage was one of the original certified while George W. Bush was president.

The researchers treat the cells with their own cocktail of growth chemicals that coax them into becoming spinal cord neural stem cells, which cant become any other kind of cell besides types of spinal cord cells.

When these cells are placed at the injury site, with or without the implant, the stem cells complete development.

Importantly, these cells grow axons, the long fibers that carry nerve signals, Tuszynski said. They extend out of the implant and into the spinal cord below the injury. They relay signals that cross synapses, the tiny gaps between nerve cells.

Because the cells arent from the patient, the body may tend to reject them. So patients receiving these cells will need immunosuppressive therapy, he said.

Newer classes of immune-suppressing drugs now available are safer and better tolerated than earlier ones, Tusyznski said.

We think patients would stay on them for awhile, he said.

The research was funded by the National Institutes of Health; the California Institute for Regenerative Medicine; and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation.

UCSD also hosts ongoing stem cell-based clinical trials for spinal cord injuries and other diseases. More information can be found at the Sanford Stem Cell Clinical Center, reachable at j.mp/ucsdssc.

Related reading

3D printed implant promotes nerve cell growth to treat spinal cord injury

Biomimetic 3D-printed scaffolds for spinal cord injury repair

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Stem cell-based spinal cord therapy expanded to more patients

Stem cells have become keys to unlock how life develops

UCSD finds possible treatment for paralysis

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