Neural tissue transplantation, repair, and rehabilitation

Transplants of cells and tissues to the central nervous system of adult mammals can, under appropriate conditions, survive, integrate, and function. In particular, the grafted cells can sustain functional recovery in animal models of a range of neurodegenerative conditions including genetic and idiopathic neurodegenerative diseases of adulthood and aging, ischemic stroke, and brain and spinal cord trauma. In a restricted subset of such conditions, cell transplantation has progressed to application in humans in early-stage clinical trials. At the present stage of play, there is clear evidence of clinical efficacy of fetal cell transplants in Parkinson disease (notwithstanding a range of technical difficulties still to be fully resolved), and preliminary claims of promising outcomes in several other severe neurodegenerative conditions, including Huntington disease and stroke. Moreover, the experimental literature is increasingly suggesting that the experience and training of the graft recipient materially affects the functional outcome. For example, environmental enrichment, behavioral activity, and specific training can enhance the recovery process to maximize functional recovery. There are even circumstances where the grafted cells have been demonstrated to restore the neural substrate for new learning. Consequently, it is not sufficient to replace lost cells anatomically; rather, for the grafts to be effective, they need to be integrated functionally into the host circuitry, and the host animal requires training and rehabilitation to maximize function of the reconstructed graft-host circuitry. Such observations require reconsideration of the design of the next generation of clinical trials and subsequent service delivery, to include physiotherapists, cognitive therapists, and rehabilitation experts as core members of the transplant team, along with the neurologists and neurosurgeons that have conventionally led the field.