Neuron-Innervated Assembloids via Free-Floating 3D Culture
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Solution Overview
Problem
Existing methods for innervating organoids lack versatility and require advanced bioengineering capabilities, making it difficult to adapt neural regulation for various organ types and perform cell type-specific genetic manipulations.
Innovation Solution
A simple and versatile method for innervating organoids by combining dissociated neuron progenitor cells with dissociated tissue progenitor cells in free-floating 3D culture, allowing self-organization into assembloids without specialized instruments or scaffolds, using neuron progenitor cells like sympathetic, parasympathetic, and sensory neurons, and tissue progenitor cells such as heart, lung, kidney, and liver cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If advanced bioengineering capabilities and specialized instruments are used to innervate organoids, then the reliability of neural regulation is improved, but the device complexity and ease of manufacture deteriorate
Solution Approach 1:
The organoid system performs self-innervation through endogenous neural progenitor cells that naturally differentiate and form neural connections within the organoid structure, eliminating the need for external bioengineering intervention. The organoid's own cellular components carry out the neural regulation function autonomously.
Solution Approach 2:
The patent extracts and removes the need for specialized bioengineering instruments and complex external neural regulation systems by utilizing the organoid's inherent capacity to generate and organize neural tissue internally through standard culture conditions.
2Adaptability or versatility
If organ-specific neural progenitor cells are used for innervation, then the adaptability to specific organ types is improved, but the ease of manufacture and versatility deteriorate
Solution Approach 1:
A single universal culture protocol is established that works across multiple organoid types (intestinal, cardiac, lung, liver, kidney) without requiring organ-specific neural progenitor cell sources. The same methodology achieves innervation in diverse organ systems, demonstrating multi-functionality.
Solution Approach 2:
The patent segments the neural development process into standardized stages that can be applied universally: (1) co-culture of organoid progenitors with neural progenitors under defined conditions, (2) spontaneous neural differentiation and migration, and (3) functional integration. This segmented approach simplifies the protocol while maintaining adaptability.
3Productivity
If one-pot differentiation protocols are used to generate neural tissue, then the productivity is improved, but the ease of operation and measurement precision deteriorate
Solution Approach 1:
Neural progenitor cells are prepared and characterized in advance before being introduced to the organoid culture system. This preliminary preparation allows for genetic manipulations to be performed on a smaller scale with better control, while the subsequent co-culture process efficiently generates the neural tissue needed for innervation.
Data Source
AI summary
Methods of making assembloids, the assembloids, compositions made from and/or including assembloids, and methods of using the foregoing are provided. Methods of making assembloids typically include combining dissociated neuron progenitor cells with dissociated tissue progenitor cells and culturing them under free floating 3D culture conditions suitable for the neuron progenitor cells and tissue progenitor cells to form one or more assembloids. In some forms, the assembloids are cultured under suitable conditions and duration for the neuron progenitor cells and tissue progenitor cells to mature. The neuron progenitor cells can be, for example, sympathetic neuron progenitor cells, parasympathetic neuron progenitor cells, and/or sensory neuron progenitor cells. The tissue progenitor cells can be, for example, heart, lung, kidney, liver, salivary gland, skin, and/or gastro-intestinal progenitor cells. Assembloids are also provided, as are compositions including assembloids, and conditioned media formed from assembloids.