Neonatal Desensitization for the Study of Regenerative Medicine

Abstract

Cell replacement is a therapeutic option for numerous diseases of the CNS. Current research has identified a number of potential human donor cell types, for which preclinical testing through xenotransplantation in animal models is imperative. Immune modulation is necessary to promote donor cell survival for sufficient time to assess safety and efficacy. Neonatal desensitization can promote survival of human donor cells in adult rat hosts with little impact on the health of the host and for substantially longer than conventional methods, and has subsequently been applied in a range of studies with variable outcomes. Reviewing these findings may provide insight into the method and its potential for use in preclinical studies in regenerative medicine.

Spontaneous Graft‐Induced Dyskinesias Are Independent of 5‐HT Neurons and Levodopa Priming in a Model of Parkinson's Disease

“…The use of neonatal desensitization makes this the first behavioral study of extended (12 months) human vmDA graft survival times in immunologically intact animals (in the absence of immunosuppression). Graft survival was low in this study (n = 4 grafts/group), but variability within this model has been reported previously 32,33 . Moreover, all published literature using this model has reported graft survival for a maximum of 6 months post‐graft 20,22 .…”

“…Graft survival was low in this study (n = 4 grafts/group), but variability within this model has been reported previously. 32 , 33 Moreover, all published literature using this model has reported graft survival for a maximum of 6 months post‐graft. 20 , 22 The data presented here are, to our knowledge, the first report of human‐to‐rat graft survival up to 12 months post‐graft.…”

The Host Immune Response to Tissue-Engineered Organs: Current Problems and Future Directions

“…The immune response mounted against stem cells often hampers in vivo investigations. Current research has recognised the need for immune modulation in order to carry out these transplantations in animal models [137]. Two recent reports have demonstrated conflicting results with neonatal tolerance to xenografts in rats.…”

Taming the Lion: The Challenge of Immunity in Regenerative Medicine

“…Nevertheless, longterm use of immune suppression may prejudice the outcome of such experiments, especially in instances where behavioral measures form the best readouts of success, since these may be significantly affected by declining health status caused by side effects of the immune suppressive regime. It is against this backdrop that the Special Report by Roberton and colleagues discusses the simple method of neonatal desensitization in which the administration of human cells to rats during the neonatal period comprehensively intervenes in the rejection of human tissues implanted later in life, permitting their functional integration to be assessed without the confounding impact of an aggressive xenogeneic response [4].…”