Cell therapeutics have entered into an exciting era, with first-in-person clinical trials underway for Parkinson's disease and novel cell therapies in development for other neurodegenerative diseases. In the hope of ensuring successful translation of these novel cell products to the clinic, a significant amount of preclinical work continues to be undertaken. Rodent models of neural transplantation are required to thoroughly assess the survival, safety and efficacy of novel therapeutics. It is critical to produce robust and reliable preclinical data, in order to increase the likelihood of clinical success. As a result, significant effort has been driven into generating ever more relevant model systems, from genetically modified disease models to mice with humanized immune systems. Despite this, several challenges remain in the quest to assess human cells in the rodent brain long-term. Here, with a focus on models of Parkinson's and Huntington's disease, we discuss key considerations for choosing an appropriate rodent model for neural transplantation. We also consider the challenges associated with long-term survival and assessment of functional efficacy in these models, as well as the need to consider the clinical relevance of the model. While the choice of model will be dependent on the scientific question, by considering the caveats associated with each model, we identify opportunities to optimize the preclinical assessment and generate reliable data on our novel cell therapeutics.
Keywords: Animal models; Cell therapy; Dopamine; Graft; Huntington's disease; Medium spiny neurons; Parkinson's disease; Stem cells; Transplantation.
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