Thesis

Transplantation of human neural progenitor cells reveals structural and functional improvements in the spastic han-wistar rat model of ataxia

Background: In this study, we assessed the ability of human neural progenitor cells (hNPC) to repair and restore the function of dying neurons within the spastic Han-Wistar rat (sHW), the mutant variant of a normal Han-Wistar. The sHW rat suffers from neurodegeneration of specific neurons, including cerebellar Purkinje cells and hippocampal CA3 pyramidal cells. The sHW rat experiences symptoms of fore limb tremor, hind leg rigidity, gait abnormality, motor incoordination, muscle wasting, and a shortened lifespan, which are akin to those seen in human ataxia patients. To alleviate the symptoms of neurodegeneration and to replace dying neurons, neuronal human progenitor cells were implanted into the sHW rats. Methods: At 30 days of age, male sHW rats underwent subcutaneous implantation of an Alzet osmotic pump that infused cyclosporine (15 mg/kg/day) used to suppress the rat's immune system. At 40 days, sHW rats received bilateral injections of live human NPCs (hNPC), dead human NPCs (dNPC), live human embryonic kidney cells (HEK), or growth media (MED) either into the cerebellar cortex or hippocampus. To monitor results, motor activity scores (open field testing) and weights of the animals were recorded. Results: The sHW rats that received hNPC transplantation into the cerebellum, at 60 days of age, displayed significantly higher motor activity scores and sustained a greater weight (both p<0.05) than dNPC, HEK, MED treated sHW rats or any hippocampal group. Along with activity scores and weight, the hNPC cerebellum treatment groups elicited greater longevity (p<0.05). Conclusion: This study reveals that implanted human progenitor cells reduce the ataxic symptoms in the sHW rat, identifying a future clinical use of these progenitor cells against neurodegenerative diseases.

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