In-vitro cochlea micro-organ functional unit and three-dimensional construction method and application thereof

Abstract

The invention discloses an in-vitro cochlea micro-organ functional unit and a three-dimensional construction method and application thereof. Separated single mouse cochlear precursor cells are subjected to three-dimensional induction culture to form cochlear organs, the cochlear organs and spiral neuron tissues are subjected to three-dimensional co-culture, and meanwhile, the cochlear organs are induced to be differentiated and mature into hair cells and promote growth of spiral neurons, so that a cochlear micro-organ functional unit with synaptic connection between hair cells and spiral neurons is constructed. The cochlear micro-organ functional unit provides a new thought and a good application model for auditory function reconstruction, and is used for researching a regulation and control mechanism of functional synapses formed by regenerated hair cells and spiral neurons; and a series of problems such as an inner ear development mechanism, a hair cell and spiral ganglion neuron damage mechanism and intervention measures, hair cell regeneration regulation and control and auditory function reconstruction are better researched.

Description

technical field [0001] The invention belongs to the field of three-dimensional culture of stem / precursor cells, and in particular relates to a three-dimensional construction method of cochlear micro-organ functional units in vitro. Background technique [0002] According to the statistics of the World Health Organization in 2019, there are currently about 466 million hearing-impaired patients in the world, accounting for more than 5% of the total population, and this number is still growing at a rate of hundreds of thousands or even millions every year. In my country, deafness is the second most disabling disease after physical disability, which not only affects the quality of life of patients, but also brings a heavy burden to families and society. The current research shows that the irreversible damage and loss of cochlear hair cells and spiral ganglion neurons are the main causes of sensorineural deafness, so exploring the mechanism of inner ear damage and intervention me...

AI Technical Summary

Problems solved by technology

[0005] At present, there are some unsolved problems: in vivo cochlear hair cells form synaptic connections with spiral neurons to complete the encoding and transmission of acoustic signals, but cochlear precursor cells can only be induced to differentiate into cochlear sensory epithelial components, through Cochlear organoids cultured from cochlear precursor cells have only a single hair cell and supporting cells similar to the cochlear sensory epithelium

The technical difficulty to be overcome in the construction of innervated cochlear micro-organs lies in the lack of a co-culture system to promote the directional differentiation and maturation of cochlear organoid cells into hair cells, and at the same time promote the growth of spiral neurons and form synaptic connections with hair cells

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