Multi-Donor Organoid Compositions from Synchronized Precursor Cells
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Solution Overview
Problem
Current methods for studying drug safety and efficacy in large populations are inefficient and costly, and there is a need for a predictive in vitro system to screen for drug-induced liver injury and identify genetic disease causes in populations, particularly in vulnerable individuals.
Innovation Solution
Development of organoid compositions derived from multiple donor cells using synchronized pooled-precursor cells, achieved through synchronization conditions and directed differentiation, allowing for the creation of a representative population model for drug screening and disease analysis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If one-to-one comparison of each individual stem cell is performed, then accurate disease phenotype and drug response analysis is achieved, but time and cost become prohibitively high
Solution Approach 1:
The patent merges multiple individual stem cell lines from different donors into a single pooled organoid composition. This combining approach maintains the ability to study population-level disease phenotypes and drug responses while dramatically reducing the time and cost associated with analyzing each cell line separately. The pooled composition represents a cohort of individuals, enabling efficient screening.
Solution Approach 2:
The pooled organoid composition serves multiple functions simultaneously: it represents a population cohort for disease modeling, enables drug safety and efficacy screening, and provides a platform for identifying genetic disease causes. This multi-functional approach replaces the need for separate individual cell studies while maintaining research comprehensiveness.
2Productivity
If directed differentiation of cell populations from more than one donor is performed, then population-scale drug screening is enabled, but synchronization of growth and differentiation becomes necessary and complex
Solution Approach 1:
The patent applies specific parameter changes to synchronize the pooled precursor cells, including controlled oxygen tension (2% O2), temperature (37°C), pH (7.4), and specific growth factor concentrations. These parameter optimizations enable coordinated growth and differentiation of cells from multiple donors, making population-scale screening feasible without excessive complexity.
Solution Approach 2:
The patent performs preliminary synchronization of the pooled precursor cells before initiating directed differentiation. This pre-synchronization step ensures that cells from different donors are at comparable developmental stages, facilitating uniform differentiation responses and reducing variability during subsequent drug screening experiments.
3Reliability
If clinical trials are conducted to determine drug safety and efficacy, then accurate human response data is obtained, but the process is costly and time-consuming with potential for unnecessary injury
Solution Approach 1:
The patent creates in vitro copies of human tissue (organoids) that replicate the functional and phenotypic characteristics of actual human organs. These organoid copies can be used to predict human drug responses, allowing researchers to screen for safety and efficacy issues before conducting costly and time-consuming clinical trials, thereby reducing unnecessary injury to trial participants.
Solution Approach 2:
The patent performs preliminary drug safety and efficacy assessments using pooled organoid compositions before human clinical trials. This pre-screening approach identifies potential toxicities and ineffective compounds in advance, allowing only the most promising candidates to proceed to clinical testing, thus reducing the time, cost, and risk associated with full clinical trial programs.
Data Source
AI summary
Disclosed are compositions, in particular, organoid compositions, derived from more than one donor cell. Further disclosed are methods of making compositions, for example, organoid compositions, that comprise a differentiated cell population derived from more than one donor cell. Donor cells may include, for example, a precursor cell such as an embryonic stem cell or other precursor cell. The disclosed methods use synchronization conditions to produce a synchronized pooled-precursor cell population, which may then be differentiated into an organoid composition. Methods of using the compositions are also disclosed.