iPSC-derived Vascular Endothelial Cell Line for Tissue-Specific Organoid Production

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Solution Overview

Problem

Current methods for drug development and research using primary cell models are limited by the inability of 2D cultured cells to replicate in vivo conditions, leading to inefficiencies in drug screening and toxicity testing due to loss of cell function and species differences, with no effective method for producing high-functionality vascular endothelial cell lines or blood vessel organoids.

Innovation Solution

A method for producing a vascular endothelial cell line derived from induced pluripotent stem cells (iPSCs) by manufacturing blood vessel organoids and dissociating single vascular endothelial cells, which can be cultured in specific media to maintain high vascular differentiation efficiency and tissue specificity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If 2D cultured cells are used for drug screening, then ease of operation is improved, but reliability is worsened due to loss of cell function and inability to reflect in vivo phenomena

Engineering Contradiction:
Improveease of operationVSAvoidreliability
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent transitions from traditional 2D monolayer cell culture to 3D organoid culture systems. The 3D structure restores physiological cell-cell interactions, extracellular matrix contacts, and tissue architecture that are lost in 2D culture, thereby improving reliability while maintaining operational feasibility through standardized protocols

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

Solution Approach 2:

The patent creates in vitro organoid models that copy and replicate the structural and functional characteristics of actual human organs and tissues. These organoids serve as faithful replicas that maintain in vivo-like cellular behaviors, drug responses, and pathological features, enabling reliable preclinical testing without requiring live animal or human subjects

Inventive Principle:
Principle #26Copying

2Productivity

If non-human cells are used for drug development, then productivity is improved, but reliability is worsened due to species differences in drug action and mechanism

Engineering Contradiction:
ImproveproductivityVSAvoidreliability
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent employs induced pluripotent stem cell (iPSC) technology to generate universal human organoid models that can be derived from various human tissue sources. These human-derived organoids provide a universal platform for drug testing that eliminates species-specific variability while maintaining high productivity through scalable culture protocols and standardized differentiation protocols

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent utilizes genetic reprogramming to transform somatic cells into pluripotent stem cells and then directs differentiation into specific organoid types. By controlling differentiation parameters and culture conditions, the system generates human organoids with consistent physiological parameters that accurately reflect human drug responses, eliminating the need for species extrapolation

Inventive Principle:
Principle #35Parameter changes

3Manufacturing precision

If primary cell models are used, then manufacturing precision is improved, but loss of substance occurs due to cell death and limited lifespan during culture

Engineering Contradiction:
Improvemanufacturing precisionVSAvoidloss of substance
Core Design Contradiction:
Manufacturing precisionVSLoss of substance

Solution Approach 1:

The patent employs primary cell-derived iPSCs that possess intrinsic self-renewal capabilities. These cells can autonomously maintain themselves through self-replication and self-differentiation into the desired organoid types, eliminating the need for continuous external intervention or supplementation while maintaining manufacturing precision and preventing cell loss

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The patent performs genetic reprogramming and expansion of primary cells into iPSC lines before differentiation into organoids. This preliminary action creates a renewable cell source with extended lifespan and enhanced stability, preventing subsequent cell death and loss during the organoid production process while maintaining the physiological characteristics of the original primary cells

Inventive Principle:
Principle #10Preliminary action

Data Source

PatentUS20240409904A1Protocol generating tissue specific endothelial cell line, named liovecs (lung tissue ipsc origin vessel organoid endothelial cell) and biovecs (blood vessel stem cell ipsc origin vessel organoid endothelial cells)
Publication Date: 2024.12.12 THE CATHOLIC UNIV OF KOREA IND ACADEMIC COOP FOUND
  • US20240409904A1 patent drawing
  • US20240409904A1 patent drawing
  • US20240409904A1 patent drawing

AI summary

The present invention relates to a method of developing a tissue-specific vascular endothelial cell line based on iPSCs derived from human tissue-specific cells. When an organoid is manufactured using the cell line based on the iPSCs derived from human tissue-specific cells, the organoid manufacturing period may be significantly shortened, thereby solving the problem of sustainability, which is a major drawback known in the related art, and may be stored conveniently, and thus may be easily used during each experiment, thereby greatly increasing efficiency. Also, the organoid manufactured from the cell line of the present invention may be usefully used in the manufacture of blood vessel organoids in that the organoid is not only tissue-specific but also exhibits an excellent level of morphological and functional maturity.