In Vitro Culture Duration does Not Impact the Ability of Encapsulated Choroid Plexus Transplants to Prevent Neurological Deficits in an Excitotoxin-Lesioned Rat Model of Huntington's Disease

Abstract

Delivery of neurotrophic molecules to the CNS is a potential treatment strategy for preventing the neuronal loss accompanying many neurological disorders. Choroid plexus (CP) epithelial cells secrete a cocktail of neurotrophic factors, and encapsulated CP transplants are neuroprotective in animal models of stroke and Huntington's disease (HD). Prior to clinical use, it is essential to identify and optimize parameters such as the length of time that transplant products such as encapsulated CP can be maintained. In the present study, neonatal porcine CP was encapsulated within alginate microcapsules and maintained in vitro for 1, 2, or 7 months. The encapsulated cells remained viable (>80%) at all time points and were transplanted unilaterally into the rat striatum. Seven days later, the same animals received unilateral injections of quinolinic acid (QA; 225 nmol) adjacent to the implant site. Separate groups of animals served as controls and received QA alone. After surgery, animals were periodically evaluated for weight loss and were tested for motor function 14 days post-QA. In controls, QA lesions produced a significant loss of body weight and impaired function of the contralateral forelimb. In contrast, implants of CP were potently neuroprotective as rats receiving CP transplants did not lose body weight and were not significantly impaired when tested for motor function. These benefits were independent of the length of time that the cells were held in vitro and demonstrate that the potential potency of alginate encapsulated CP cells can be retained for extremely long periods of time in vitro.