Human Stem Cell-Derived Neurons Grow New Axons In Spinal Cord Injured Rats

A stem cell-based treatment for spinal cord injury took one more baby step forward when scientists from the laboratory of Mark Tuszynski at the at the University of California, San Diego used cells derived from an elderly man’s skin to regrow neural connections in rats with damaged spinal cords.

Tuszynski and others published their results in the Aug. 7 online issue of the journal Neuron. In that paper, Tuszynski and his co-worker report that human stem cells triggered the growth of numerous axons in the damaged spinal cord. Axons are those fibers that extend from the main part or body a neuron (nerve cell) that serve to send electrical impulses away from the body to other cells. Some of these new axons even grew into the animals’ brains.

Axon picture

Dr. Mark Tuszynski is a professor of neurosciences at the University of California, San Diego. “This degree of growth in axons has not been appreciated before,” he said. However, Tuszynski also cautioned that there is still much to be learned about how these newly established nerve fibers behave in laboratory animals. He likened the potential for stem-cell-induced axon growth to nuclear fusion. If it’s contained, you get energy; if it’s not contained, you get an explosion. “Too much axon growth into the wrong places would be a bad thing,” Tuszynski added.

Stem cell researchers have examined the potential for stem cells to restore functioning nerve connections in people with spinal cord injuries. Embryonic stem cells have been used to make new neurons and to also make “oligodendrocyte progenitor cells” or OPCs, which make the insulating myelin sheath that enwraps the axons of spinal nerves. However, several other types of stem cells can make OPCs and new neurons and these stem cells do not come from embryos (for more, see chapter 27 of my book, The Stem Cell Epistles).

In this study, Tuszynski and his team used induced pluripotent stem cells or iPSCs, which are derived from mature adult cells by means of genetic engineering and cell culture techniques. They used cells from a healthy 86-year-old man and genetically reprogrammed so that they were reprogrammed into iPSCs. These iPSCs were then differentiated into neurons that were implanted into a special scaffold embedded with proteins called growth factors, and then grafted into the spinal cords of laboratory rats with spinal cord injuries.

Over the course of several months, these animals showed new, mature neurons and extensive growth in the cells’ axons. These fibers grew through the injury-related scar tissue in the animals’ spinal cords and connected with resident rat neurons.

This is an enormous advance, because the wounded spinal cord creates a “Glial scar” that contains a host of molecules that repel growing axons. Even though this glial scar prevents the immune system from leaking into the spinal cord and destroying it, this same scar prevents the regeneration of damaged neurons and their severed axons.

Glial scar axon repulsion

Dr. David Langer, director of neurosurgery at Lenox Hill Hospital in New York City said: “One of the big obstacles [in this type of research] is this area of scarring in the spinal cord. Getting neurons to traverse it is a real challenge,” said Langer, who was not involved in the research. “The beauty of this study,” he said, “is that they got the neurons to survive and traverse the scar.”

Langer also cautioned, much like Tuszynski, that this experimental success is just a preliminary step. There are, in his words, “huge questions” as to whether or not these axons can make appropriate connections and actually restore function to spine-damaged lab animals. “It’s not just a matter of having the cables,” Langer said. “The wiring has to work.”

And even if this stem cell approach does pan out in animals, Langer added, it would all have to be translated to humans. “We have a long way to go until we’re there,” he said. “It’s not that people shouldn’t have hope. But it should be a realistic hope.”

A few biotech companies have already launched early-stage clinical trials using embryonic (Geron) or fetal stem cells (StemCells Inc) to treat patients with spinal cord injuries. But Tuszynski said his team’s findings offer a cautionary note about moving to human trials too quickly. “We still have a lot to learn,” he said. “We want to be very sure these axons don’t make inappropriate connections. And we need to see if the new connections formed by these axons are stable.”

Ideally, Tuszynski added, if stem cells were to be used in treating spinal cord injuries, they’d be generated as they were in this study — by creating them from a patient’s own cells. That way, he explained, patients would not need immune-suppressing drugs afterward.