In theory, a biopsy could be performed to obtain the needed olfactory ensheathing glia from a patient. But once the properties that enable them (or other cells) to be competent escorts for growing axons are determined, researchers may instead be able to genetically alter other cell types if desired, giving them the required combinations of growthpromoting properties.
Fibroblasts (cells common in connective tissue and the skin) are among those already being engineered to serve as bridges. They have been altered to produce the neurotrophic molecule NT-3 and then transplanted into the cut spinal cord of rodents. The altered fibroblasts have resulted in partial regrowth of axons. Along with encouraging axonal regrowth, NT-3 stimulates remyelination. In these studies the genetically altered fibroblasts have enhanced myelination of regenerated axons and improved hind limb activity.
Replace Lost Cells
Other transplantation schemes would implant cells that normally occur in the central nervous system. In addition to serving as bridges and potentially releasing proteins helpful for axonal regeneration, certain of these grafts might be able to replace cells that have died.
Transplantation of tissue from the fetal central nervous system has produced a number of exciting results in animals treated soon after a trauma. This immature tissue can give rise to new neurons, complete with axons that travel long distances into the recipient’s tissues (up and down several segments in the spinal cord or out to the periphery). It can also prompt host neurons to send regenerating axons into the implanted tissue. In addition, transplant recipients, unlike untreated animals, may recover some limb function, such as the ability to move the paw in useful ways. What is more, studies of fetal tissue implants suggest that axons can at times find appropriate targets even in the absence of externally supplied guidance molecules. The transplants, however, are far more effective in the immature spinal cord than in the injured adult cord—an indication that young children would probably respond to such therapy much better than adolescents or adults would.
Some patients with long-term spinal cord injuries have received human fetal tissue transplants, but too little information is available so far for drawing any conclusions. In any case, application of fetal tissue technology in humans will almost surely be limited by ethical dilemmas and a lack of donor tissue. Therefore, other ways of achieving the same results will have to be devised. Among the alternatives is transplanting stem cells: immature cells that are capable of dividing endlessly, of making exact replicas of themselves and also of spawning a range of more specialized cell types.
Various kinds of stem cells have been identified, including ones that generate all the cell types in the blood system, the skin, or the spinal cord and brain. Stem cells found in the human adult central nervous system have, moreover, been shown capable of producing neurons and all their accompanying glia, although these so-called neural stem cells seem to be quiescent in most regions of the system. In 1998 a few laboratories also obtained much more versatile stem cells from human tissue. These human embryonic stem cells (in common with embryonic stem cells obtained previously from other vertebrates) can be grown in culture and, in theory, can yield almost all the cell types in the body, including those of the spinal cord.
Stem Cell Strategies
How might stem cells aid in spinal cord repair? A great deal will be possible once biologists learn how to obtain those cells readily from a patient and how to control the cells’ differentiation. Notably, physicians might be able to withdraw neural stem cells from a patient’s brain or spinal cord, expand the numbers of the still undifferentiated cells in the laboratory and place the enlarged population in the same person’s cord with no fear that the immune system will reject the implant as foreign. Or they might begin with frozen human embryonic stem cells, coax those cells to become precursors, or progenitors, of spinal cells and implant a large population of the precursors. Studies proposing to examine the effects on patients with spinal cord injuries of transplanting neural stem cells (isolated from the patients’ brains by biopsy) are being considered.