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Just over 20 years ago, the notion that nerve cells transplanted to a damaged adult brain could not only survive but also make functional connections would generally have been regarded as heretical. Since that time, however, the field of embryonic neural transplantation has grown almost exponentially and has emerged as a credible discipline. Aside from considerations of functional repair to brain damaged hosts, the technique has also been revolutionary as a tool for investigating neural development and specific aspects of neurodegeneration.
This Neuromethods volume is the 36th in an ongoing series and has an internationally acclaimed neuroscientist as first editor. In particular, Professor Stephen Dunnett was instrumental in establishing embryonic neural transplantation as an experimental technique from its earliest days in the late 1970s and has remained its leading scientific figure in the United Kingdom. The volume itself is clearly devised as a handbook for aspiring neural transplant surgeons or those wishing to hone their techniques. Rather than serving merely as a manual, however, it also provides a timely historical review and exhaustive reference source for this young science. It is divided into three sections which, respectively, focus on the numerous possibilities for obtaining neural cells for transplantation, the techniques of implanting the neural tissue, and, lastly, tips for enhancing neuronal survival and connectivity.
The first of these aspects is perhaps the most controversial, especially with respect to potential clinical applications for neural transplantation in Parkinson's and Huntington's diseases. It has been abundantly clear from the earliest use of this technique in human patients that obtaining embryonic tissue would provide extreme practical problems and cause the most ethical concern. It is extremely useful, therefore, to find up to date chapters on neural stem cells, immortalised cell lines, and engineered cells as sources for transplant material. Similarly, the chapter on intracerebral gene transfer using various viral vectors provides an alternative approach to studying development and even repair, representing a potentially exciting tool for the future.
The section on transplant methods serves as a useful review of a technique for introducing transplant material to the host. It also includes a chapter on glial transplants as an experimental method for the remyelination of central nervous tissue. In general, this section draws on the considerable experience from the leading laboratories in the field and underlines the expertise required to undertake successful grafting using techniques which, to the uninitiated, may seem deceptively simple. In addition, one chapter revisits the early technique of intraocular grafting which, as an in vivo model, has several advantages. In particular, the accessibility and ease of visualising graft growth in this model allows many of the basic scientific questions on neural transplantation to be addressed.
The final section on the factors governing graft survival and function is, by necessity, perhaps the most speculative. The reason why over 90% of grafted embryonic neurons fail to survive remains largely obscure and is almost certainly multifactorial, reflecting host and graft factors. The potential role of apoptosis is discussed in some detail as are the various methods of inhibiting this process by specific means such as captase inhibition or the use of trophic factors. The chapter by Brundin explores the nature and timing of transplant cell death and includes discussion of antioxidant strategies. The potential utility of combining several neuroprotective approaches is pertinently addressed. Several other chapters in this section centre on the difficult issue of immunological rejection of transplant tissue by the host. The likely need for genetically engineered transplant tissue for successful grafting across species is discussed despite the relatively low immunogenicity of embryonic neural tissue and the (semi) privileged transplant sites within the blood-brain barrier. These issues are particularly pertinent to the potential clinical use of embryonic porcine neural tissue in human neurodegenerative disease.
In conclusion, this book provides an exhaustive summary of the neurobiological theory and techniques, both established and potential, relating to neural transplantation. It is clearly a highly specialised area now emerging from its infancy and is unlikely to have general appeal to clinical neurologists. However, certainly for those intending to use this immensely powerful technique in the context of basic neuroscientific research, the book will be invaluable. Similarly, for those with an interest in the potential application of neural (or glial) grafting in human disease, the volume will provide an excellent rationale for the technique and give a state of the art account of where we stand. The illustrations are generally of extremely high quality and the references extend to 1999. If the volume is read sequentially there is a degree of repetition among the numerous authors but this would be my only quibble. If the field of neural transplantation “takes off” in the decades to come, as many think, this volume is likely to find itself a classic, heralding the definitive arrival of this novel and innovative technique.
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