tissue surrounding the heart—may give rise to neuronal cells; and numerous research avenues need to be explored. Additionally, there is much to learn about the mechanisms that direct stem cells to differentiate and mature (e.g., plasticity, fusion, and transdifferentiation), and it is likely that the observations of the mechanism of action from the study of stem cell-based therapies for a wide range of health outcomes will be able to be directly translated to the development of therapeutic interventions to promote spinal cord repair and regeneration.

DEVELOPING NEW INTERVENTIONS AND COMBINATION THERAPEUTIC STRATEGIES

This chapter and others have identified many possible targets for therapeutic interventions and many possible therapeutic approaches. As researchers gain additional insights into the mechanisms of neuronal repair and regeneration, efforts to move these discoveries into clinically meaningful therapies will continue.

One of the major themes arising from this chapter is that, owing to its complexity, a spinal cord injury is unlikely to be cured by a single therapy. The biological processes involved in regaining sensory or motor functions, preventing or eliminating pain, and retraining and relearning motor tasks are so diverse that treatment strategies that use a combination of therapies will almost certainly be required. A balance between destructive and regenerative events in the aftermath of a spinal cord injury dictates the clinical course and outcome; therapeutic approaches will likewise need to address the multiple and complex therapeutic targets and health problems. This is analogous to childhood leukemia, once a uniformly fatal disease. Investigators tested one drug after another, with only marginal effects on life expectancy. Ultimately, a carefully crafted combination of drugs resulted in a total cure rate of more than 50 percent (NAS, 1997).

In light of the complicated dynamics, some of the most promising and intriguing studies that were recently published and are described in this chapter have drawn on the combined potencies of more than one therapy. One study, for example, showed that a combination therapy that targets both the neuronal cell body and its axons was more effective than either therapy alone (Lu et al., 2004). Another study implanted scaffolds seeded with stem cells (Teng et al., 2002). The concept behind that study was that the scaffold would set the stage by providing a conduit for growth and the stem cells would release soluble factors to stimulate growth. With the combination, axons regrew and restored some of the lost function. A third study boosted the cell-signaling molecules needed for axon regrowth and replacement of myelin. It showed that functional recovery could be achieved with rolipram, which boosts cyclic AMP levels, combined with an injection



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