Building a Bridge to Therapies: Stem Cell-Derived Neurons Restore Feeling to Injured Limbs

It’s been a great week for spinal cord injury-related stem cell research – and it’s only Tuesday. In case you missed it, Asterias Biotherapeutics announced yesterday that they had treated their first clinical trial participant with an embryonic stem cell-based therapy for complete spinal cord injury. “Complete” refers to injuries that cause a total loss of feeling and movement below the site of injury.

Transplant human neurons (red) provide a bridge for the mice nerve fibers (green) to enter the spinal cord (spc). Image credit Hoeber et al. Scientific Reports

Transplanted human neurons (red) provide a bridge for the mice nerve fibers (green) to enter the spinal cord surface (spc). Image credit: Hoeber et al. Scientific Reports 5:10666

In another study also reported yesterday in Nature’s Scientific Reports, researchers at Uppsala University in Sweden made significant progress toward understanding and treating a related but different sort of injury that disrupts nerve signals coming into and out of the spinal cord. These so-called avulsion injuries are frequently seen after traffic, particularly motorcycle, accidents and lead to paralysis, loss of sensation, and chronic pain in the affected limbs. Although the ruptured nerve fibers from the limbs have the ability to extend back toward the spinal cord, inflammation from the site of injury makes the spinal cord impenetrable and blocks any restoration of normal sensory function.

To explore the potential of overcoming this spinal cord barrier, the research team transplanted human embryonic stem cell-derived neurons into mice mimicking human avulsion injury. Five months after the transplant, growth of nerve fibers into the spinal cord was seen. But these nerve fibers that had reconnected with the spinal cord were host animal cells and not the transplanted human stem cell-derived neurons. It turns out the human neuron fibers provide a physical bridge permitting the mouse nerve fibers to extend into the spinal cord. The human neurons also encourage this regrowth by releasing proteins that reduce the scar left by the injury and promote nerve fiber growth. The reconnected nerve fibers is an exciting result but did it have any impact on the animals? The answer is yes. Using standard behavior tests the team found that injured mice with the transplanted neurons had more sensitivity to touch stimulation and greater grip strength compared to untreated injured mice.

Because stem cells have the ability for unlimited growth, any future therapy based on these findings must shown that the transplant doesn’t lead to excessive cell growth. In an encouraging sign, no tumor formation or extreme growth of human neurons in the animals were observed.

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