Cell Type Counts in Spinal Therapy

Rats regain motor skills with one kind of cell transplant, get nerve pain with another.

Small differences in the type of cells used for transplantation therapies can have a big impact on outcome. In experiments published in the current edition of the Journal of Biology, scientists from the University of Rochester and the University of Colorado found that transplanting a certain type of cell improved motor function in rats whose spinal cords had been severed. However, transplantation of a closely related cell type had little benefit and actually made the animals more sensitive to pain.

Starring role: A specific type of astrocyte--star-shaped support cells found in the central nervous system--may have healing effects for spinal cord injuries. Researchers grew astrocytes (green) from embryonic stem cells and found they improved motor function in rats with injured spinal cords. Credit: Stephen Davies/University of Colorado

The findings illustrate the importance of differentiating stem cells before transplanting them into injured tissue, an issue that has been under great debate as stem cell-based therapies approach human testing. "This study demonstrates for the first time the dynamics of developmentally different populations of [cells], which we need to take into account," says Martin Marsala, a professor of anesthesiology who teaches at the University of San Diego and was not involved in the study.

Stem cells have the potential to grow into new neurons and other cell types, a property scientists aim to exploit to treat spinal cord injury. Transplanted cells might bridge severed nerves in the spinal cord or encourage recovery of existing cells. However, scientists working toward this goal have run into two main problems: stem cells transplanted into the spinal cord have a hard time forming lasting neurons, and these same cells tend to induce nerve-related pain.

One problem is that transplanting undifferentiated, or "naïve," stem cells into injured tissue cells tends to cause the formation of scar tissue, instead of regenerating healthy neurons, says Stephen Davies, associate professor of neurosurgery at the University of Colorado. "It might be that scars form to protect an injury site from infection, so the injured tissue goes into lockdown mode and will recruit whatever precursor cells are present to form scars," he says. The alternative is to differentiate cells into specific cell types before transplanting them.

Davies and his associates at the University of Rochester found that the right kind of cells for repairing spinal cord injuries may be a subtype of support cells found throughout the central nervous system, called astrocytes. These star-shaped cells have various forms and functions, but are largely involved in providing nutrients to the brain and repairing injury.

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To test their healing potential, Davies' team grew two different kinds of astrocytes from the same line of embryonic stem cells by exposing them to different cocktails of signaling molecules--molecules that stimulate stem cells to grow into specific cells. One sample yielded astrocytes that were flat and broad, called GDAbmp. The other produced more elongated astrocytes, called GDAcntf.

The researchers then surgically severed rats' spinal cords at the base of the neck--a common location of spinal injury in humans--and injected the animals with naïve stem cells, stem cell-derived GDAbmp, and stem cell-derived GDAcntf.