Retinal-Cortical Assembloids for Axon Extension

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Solution Overview

Problem

Current methods for differentiating retinal ganglion cells from human pluripotent stem cells lack the organization and ability to extend axons across long distances, limiting their utility as models for retinal development and cell replacement therapies for retinal degenerative diseases.

Innovation Solution

The development of three-dimensional neural tissue compositions, specifically retinal-cortical assembloids, which fuse retinal organoids with cortical and thalamic organoids to facilitate elongated axon growth and mimic in vivo retinal development, enhancing the differentiation and survival of retinal ganglion cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If retinal ganglion cells are differentiated from human pluripotent stem cells in a stochastic manner, then the differentiation process is simple and rapid, but the resulting RGCs lack organization and cannot extend axons across long distances

Engineering Contradiction:

Improvedifferentiation efficiencyVSAvoidaxon extension capability

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent combines retinal organoids with cortical and thalamic organoids to form assembloids, merging multiple tissue types to enable RGCs to extend axons across long distances to target regions while maintaining efficient differentiation

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The patent transitions from two-dimensional cultured RGCs to three-dimensional assembloid structures, enabling axons to extend through spatial depth and reach distant targets while maintaining organizational structure

Inventive Principle:

Principle #17Another dimension (Dimensionality change)

2Ease of manufacture

If retinal organoids are cultured alone, then the culture system is simple and maintenance is easy, but the retinal area and cell proliferation are limited

Engineering Contradiction:

Improveculture system simplicityVSAvoidretinal area and cell proliferation

Core Design Contradiction:

Ease of manufactureVSQuantity of substance

Solution Approach 1:

The patent merges retinal organoids with cortical and thalamic organoids in assembloids, combining the proliferative capacity of multiple tissue types to increase overall retinal area and cell proliferation while maintaining manageable culture conditions

Inventive Principle:

Principle #5Merging (Combining)

3Loss of time

If stochastic differentiation methods are used, then the process is fast and straightforward, but the RGCs lack the organization typical of the retina and cannot respond appropriately to extrinsic guidance cues

Engineering Contradiction:

Improvedifferentiation timeVSAvoidtissue organization and guidance response

Core Design Contradiction:

Loss of timeVSManufacturing precision

Solution Approach 1:

The patent performs preliminary organization of retinal structures and guidance cue placement before RGC differentiation completes, enabling RGCs to develop with proper tissue organization and responsiveness to extrinsic cues while maintaining relatively fast differentiation timing

Inventive Principle:

Principle #10Preliminary action

Data Source

PatentUS20220387513A1Compositions and methods for enhancing retinal ganglion cell development and pluripotent stem cell-derived three-dimensional tissue

Publication Date: 2022.12.08 THE TRUSTEES OF INDIANA UNIV

AI summary

Various aspects and embodiments disclosed herein relate generally to the stem cell biology and cell replacement therapy. Embodiments include compositions and methods for modelling, treatment, reducing resistance to the treatment, prevention, and diagnosis of a condition/disease associated with retinal degenerative diseases or a related clinical condition thereof. Other embodiments include methods and compositions for developing pluripotent stem cell-derived 3D tissues.