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Is There a Future for Neural Transplantation?

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Abstract

Traditionally neural transplantation has had as its central tenet the replacement of missing neurons that have been lost because of neurodegenerative processes, as exemplified by diseases such as Parkinson disease (PD). However, the effectiveness and widespread application of this approach clinically has been limited, primarily because of the poor donor supply of human fetal neural tissue and the incomplete neurobiological understanding of the circuit reconstruction required to normalize function in these diseases. So, in PD the progress from promising neural transplantation in animal models to proof-of-principle, open-labeled clinical transplants, to randomized, placebo-controlled studies of neural transplantation has not been straightforward. The emergence of previously undescribed adverse effects and lack of significant functional advantage in recent clinical studies has been disappointing and has served to cast a new, and perhaps more realistic, perspective on this treatment approach. In fact, there have been calls by some involved in neural transplantation to return to the drawing board before pressing on with further clinical trials, and the return to basic experimentation. This therefore precipitates the question — is there a future for neural transplantation?

It is important to remember that there are a number of possible explanations for the disappointing results from the recent clinical trials in PD, ranging from the mode of transplantation to patient selection. Nevertheless, almost irrespective of these reasons for the current trial results, there have always been significant practical and ethical problems with using human fetal tissue, and so a number of alternative cell sources have been investigated. These alternative sources include stem cells, which are attractive for cell-based therapies because of their potential ease of isolation, propagation and manipulation, and their ability in some cases to migrate to areas of pathology and differentiate into specific and appropriate cell types. Furthermore, the availability of stem cells derived from non-embryonic sources (e.g. adult stem cells derived from the sub-ventricular zone) has removed some of the ethical limitations associated with the use of embryonic human tissue. These potentially beneficial aspects of stem cells means that there is a future for neural transplantation as a means of treating patients with a range of neurological disorders, although whether this will ever translate into a truly effective, widely available therapy remains unknown.

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Acknowledgements

Dr Harrower was a Wellcome Clinical Training Fellow and was additionally supported by the Sackler Foundation, the D R Macintosh trust, and received a Brain Scholarship from the Guarantors of Brain. The Parkinson’s Disease Society (PDS) and the Medical Research Council of the United Kingdom supported some of our work cited in this review.

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  1. Cambridge Centre for Brain Repair, Forvie Site, Robinson Way, Cambridge, CB22PY, UK

    Timothy P. Harrower & Roger A. Barker

  2. Department of Neurology, Addenbrooke’s Hospital, Cambridge, UK

    Timothy P. Harrower & Roger A. Barker

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  1. Timothy P. Harrower
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  2. Roger A. Barker
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Correspondence to Timothy P. Harrower.

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Harrower, T.P., Barker, R.A. Is There a Future for Neural Transplantation?. BioDrugs 18, 141–153 (2004). https://doi.org/10.2165/00063030-200418030-00001

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