Chapter 55: neural transplantation

The history of cell transplantation in the nervous system is reviewed in four main sections. The "early era" spans the period from 1890 to 1940, during which the first attempts at cell transplantation in the brain were undertaken. Many contemporary themes were first addressed such as surgical factors to achieve survival of grafted cells and how that should be assessed, immunological factors, use of tumors as a readily viable cell source; and use of the anterior eye chamber as a model transplantation site. However, such studies generally exhibited only low levels of viability or successful implantation. The "middle era" from 1940 to 1970 spans the period when the techniques for viable and reliable cell transplantation using embryonic donor tissues implanted into sites with effective vascularization were first established in brain and neuroendocrine systems in a limited number of specialist centers. However, although sometimes impressive, these results were at variance with the prevailing view that the adult mammalian brain is immutable and resistant to plasticity, growth or regeneration, and were largely ignored. The "modern era," since 1970, began with the pioneering studies that combined cell transplantation with the use of improved histochemical and ultrastructural anatomical techniques to demonstrate selectivity, specificity and regenerative capacity of implanted cells, and the slow acceptance that the adult brain does exhibit considerable potential for plasticity and repair. The last three decades have witnessed the identification of reliable and efficient transplantation technologies combined with progressively refined methods of molecular, cellular, biochemical, physiological and functional analysis. This now enables the ready use of cell transplantation as a powerful novel method within the neuroscience tool-kit, which is being used: to analyze normal organization and function of the nervous system; to reveal the biological mechanisms and principles of neuronal development, regeneration and plasticity; and to study the principles of surgically directed cell therapies for promoting plasticity, replacement and repair in response to injury and disease. The final section reviews recent progress in translating cell transplantation to the clinic for application in Parkinson's and other central nervous system diseases.