Cell Replacement Therapy: Helping the Brain to Repair Itself

Abstract

The interest in cell replacement therapies for human CNS disorders dates back to the late 1970s, when it was demonstrated that intrastriatal grafts of fetal mesencephalic tissue, rich in dopamine neurons, induced functional recovery in rats with neurotoxin-induced lesions of the nigrostriatal dopaminergic system. These observations provided the first evidence that neurons implanted into the adult brain could reverse behavioral deficits in an animal model of a human neurological disorder, Parkinson’s disease. Based on a bulk of experimental data in rodents and nonhuman primates, the first clinical trials with neural transplantation in Parkinson’s disease were initiated in 1987. Successful studies in animal models of Huntington’s disease led to the first attempts with fetal striatal grafts in Huntington’s disease patients in the late 1990s. In addition, neural transplantation has also been applied clinically, with varying degree of scientific foundation, in other disorders such as stroke and epilepsy, and in patients with spinal cord injury. The basic principle of cell therapy is quite simple: restoration of function lost as a result of damage or disease in the CNS by the replacement of dead cells with new healthy ones. Given the complexity of both the structure and function of human brain and spinal cord, this prospect may seem remote. In fact, until 25 years ago, the possibility of using cell replacement for CNS repair was regarded as science fiction. Today, cell therapy is a realistic therapeutic possibility. Extensive animal experimental studies performed over the last two decades have shown that neuronal replacement and partial reconstruction of neuronal circuitry is indeed feasible. If this approach can be made to work in the human nervous system, cell therapy could provide radical new treatments for severe neurological disorders. These emerging prospects raise a number of scientific and ethical concerns. First, the rationale for the application of cell therapy may not be equally good for all types of brain damage, and for some more complex CNS disorders the usefulness of the cell repair strategy remains highly speculative. Secondly, the rush to apply cell therapies in patients may lead to scientifically ill-founded clinical trials without sufficient support of rigorous preclinical research.