METHOD FOR DIFFERENTIATING PLURIPOTENT STEM CELLS INTO DOPAMINERGIC NERVE CELLS IN MIDBRAIN SUBSTANTIA NIGRA

摘要

Provided is a specific method for differentiating pluripotent stem cells into dopaminergic (A9 mDA) nerve cells in the midbrain substantia nigra. Mature A9 mDA neurons are formed by means of differentiation, which can express the surface molecular markers of the dopaminergic neurons in the midbrain substantia nigra, comprising TH, FOXA2, EN1, LMX1A, NURR1 and GIRK2, but which rarely express the marker CB of the dopaminergic neurons in the ventral tegmental area. The A9 mDA nerve cells are transplanted into the substantia nigra, and the axons thereof can specifically project to the target brain area innervated by endogenous substantia nigra dopaminergic neurons, i.e. the dorsal striatum; the transplanted A9 mDA neurons themselves exhibit the classic electrophysiological characteristics of the endogenous substantia nigra dopaminergic neurons, comprising a low-frequency spontaneous discharge frequency, and can induce sag by means of hyperpolarizing current stimulation; and transplanting the A9 mDA nerve cells into the substantia nigra or striatum of individuals with neurodegenerative diseases can improve dyskinesia.