Endothelial Cell Production via Genetic Programming

Solution Overview

Problem

Current methods for producing endothelial cells are inefficient due to the limited proliferative potential of primary endothelial cells and the complexity of differentiating human embryonic stem cells or induced pluripotent stem cells into endothelial lineage, which requires multiple stages and growth factors, making it time-consuming and costly.

Innovation Solution

The method involves forward programming of pluripotent stem cells by increasing the expression of endothelial programming factor genes, such as ERG and ETV2, to directly convert non-endothelial cells into endothelial cells without the need for intermediate stages, using exogenous expression cassettes and gene delivery systems like viral vectors, allowing for the production of mature endothelial cells with specific markers and functions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If human embryonic stem cells or induced pluripotent stem cells are differentiated into endothelial lineage through multiple stages with growth factors, then endothelial cells can be produced, but the process is time-consuming and costly

Engineering Contradiction:

Improveendothelial cell productionVSAvoiddifferentiation time

Core Design Contradiction:

ReliabilityVSLoss of time

Solution Approach 1:

The patent introduces endothelial programming factor genes (such as ERG, ETV2, FLI1) into pluripotent stem cells in advance, so that when differentiation is initiated, the cells already possess the genetic programming necessary for direct endothelial lineage commitment, bypassing the need for sequential growth factor additions and intermediate stages

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent extracts and isolates the key genetic determinants (endothelial programming factor genes) that are normally distributed across multiple growth factor signals and intermediate stages, concentrating their function into a single genetic intervention that directly drives endothelial differentiation

Inventive Principle:

Principle #2Taking out (Extraction)

2Reliability

If human embryonic stem cells or induced pluripotent stem cells are differentiated into endothelial lineage through multiple stages with growth factors, then endothelial cells can be produced, but the process is complex and costly

Engineering Contradiction:

Improveendothelial cell productionVSAvoiddifferentiation process complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent extracts and isolates the key genetic determinants (endothelial programming factor genes) that are normally distributed across multiple growth factor signals and intermediate stages, concentrating their function into a single genetic intervention that directly drives endothelial differentiation

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent merges the functions of multiple growth factors and intermediate differentiation stages into a single genetic intervention by introducing endothelial programming factor genes that collectively perform the roles of multiple sequential signals, simplifying the overall differentiation protocol

Inventive Principle:

Principle #5Merging (Combining)

3Reliability

If primary endothelial cells are used for therapeutic applications, then patient-specific treatment is possible, but the proliferative potential is limited

Engineering Contradiction:

Improvepatient-specific treatmentVSAvoidcell proliferation

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent introduces endothelial programming factor genes into pluripotent stem cells in advance, so that when differentiation is initiated, the cells already possess the genetic programming necessary for direct endothelial lineage commitment, bypassing the need for sequential growth factor additions and intermediate stages

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent changes the fundamental parameter of cell identity by introducing transcription factor genes that reprogram the cellular differentiation pathway, transforming pluripotent stem cells directly into endothelial cells with high proliferative capacity, thereby overcoming the limited proliferation of primary endothelial cells

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentEP2591093B1Endothelial cell production by programming

Publication Date: 2018.11.28 FUJIFILM CELLULAR DYNAMICS INC

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AI summary

The invention generally regards methods for providing endothelial cells and precursors of endothelial cells from a variety of cell sources, such as pluripotent stem cells. Also provided are therapeutic compositions including the provided endothelial cells, and methods of using them for the treatment of subjects.