NeuralCipher Research overview
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Current ectopic implantation has shown limited efficacy in promoting reinnervation of the nigrostriatal pathway, which is critically affected in Parkinson's disease (PD). Homotopic transplantation, on the other hand, may facilitate physiological cell rewiring of the basal ganglia, potentially improving PD symptoms. This study aimed to evaluate the efficacy and safety of homotopically engrafting human induced pluripotent stem cells (hiPSCs)-derived midbrain organoids into the substantia nigra of PD rats. A rat model of PD was induced using 6-hydroxydopamine (6-OHDA) and homotopically transplanted into the lesioned SN with hiPSC-derived hMOs. The engrafted hMOs survived and continually mature in host brains, and were mainly differentiated into dopaminergic lineage neurons, part of which presented TH+ fibers. Behavioral evaluation demonstrated that transplantation of hMOs gradually reverse the motor disorder caused by 6-OHDA lesioning by 22% at week 5 and 35% by week 10 post-transplantation, respectively. No tumor formation or migration was detected in either subcutaneous space or vital organs following 10 weeks implantation. These findings support the efficacy and safety of homotopical hMOs transplantation, offering a promising cell-based strategy for treating Parkinson's disease.
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