Validation and characterisation of a new method for in vivo assessment of human donor cells

Doctoral thesis English OPEN
Roberton, Victoria H.
  • Subject: RC0321

This thesis encompasses a range of experiments designed to characterise and validate a method of desensitising rodent hosts in the neonatal period to human tissue in order to promote the survival of human striatal grafts in the adult host. Thus, the successful application of this method is important to allow the preclinical testing of potential human donor cells for therapeutic transplantation, specifically in neurological disease. Demonstrating safety and functionality of transplanted human cells in rodent hosts requires long term assessment of surviving grafts, for which current immune suppression methods are insufficient. The experiments presented in this thesis were therefore designed to determine the optimum parameters of a previously described method of desensitising rats to human tissue and to validate this method in mice.\ud The findings provide further support for the neonatal desensitisation method in rat hosts, and suggest the potential for use of non-neural tissue types for desensitisation of neonates. The data presented in this thesis also has implications for the mechanisms underlying the success of the method in the rat. However interpretation was difficult as graft survival was generally poor and even mouse to mouse allografts did not survive to the level expected. Thus this highlights the need to reassess standard immunosuppression protocols in mice, and determine what differs between the rat and mouse rejection response to xenografts.
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