Iodobenzothiazolyl-phenyl-propanamide Stem Cell Differentiation

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Solution Overview

Problem

Current methods for inducing differentiation of pluripotent stem cells into cardiac muscle cells are inefficient, costly, and contaminated with feeder cells, making them unsuitable for commercial production and drug safety evaluations.

Innovation Solution

A composition containing iodobenzothiazolyl-phenyl-propanamide compounds is used to promote the differentiation of pluripotent stem cells into cardiac muscle cells without feeder cells, enhancing efficiency and reducing costs, and can be used in combination with other differentiation promoters to further enhance differentiation efficiency.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If co-culturing human ES cells and mouse feeder cells (END2 cells) is used to induce cardiac muscle cell differentiation, then differentiation can be achieved, but differentiation efficiency is not satisfactory and human cardiac muscle cells are contaminated with mouse END2 cells

Engineering Contradiction:
Improvepurity of cardiac muscle cellsVSAvoiddifferentiation efficiency
Core Design Contradiction:
Manufacturing precisionVSProductivity

Solution Approach 1:

The patent removes the harmful element (mouse feeder cells) from the differentiation system by using a defined medium composition instead of co-culture methods, thereby eliminating contamination while maintaining differentiation capability

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the chemical parameters of the differentiation environment by specifying exact concentrations of cytokines (bFGF, BMP4, VEGF, DKK1, Activin A) in a defined medium, replacing biological co-culture with controlled chemical factors

Inventive Principle:
Principle #35Parameter changes

2Manufacturing precision

If embryoid formation with multiple cytokines (bFGF, BMP4, VEGF, DKK1, Activin A) is used to induce cardiac muscle cell differentiation, then differentiation can be achieved, but the method requires a large amount of cytokines and is rather expensive

Engineering Contradiction:
Improvedifferentiation efficiencyVSAvoidcost of cytokines
Core Design Contradiction:
Manufacturing precisionVSQuantity of substance

Solution Approach 1:

The patent optimizes the concentration parameters of cytokines in the differentiation medium, using specific low concentrations (e.g., bFGF: 1-10 ng/mL, BMP4: 1-10 ng/mL, VEGF: 1-10 ng/mL, DKK1: 1-10 ng/mL, Activin A: 1-10 ng/mL) to achieve effective differentiation while minimizing cost

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses minimal effective concentrations of each cytokine rather than high concentrations, achieving sufficient differentiation signal with reduced substance quantity and lower cost

Inventive Principle:
Principle #16Partial or excessive action

3Reliability

If conventional differentiation methods are used, then cardiac muscle cells can be obtained, but the methods are not suitable for commercial production due to low efficiency and high cost

Engineering Contradiction:
Improvesuitability for commercial productionVSAvoiddifferentiation efficiency
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent establishes optimized parameter ranges for differentiation factors that balance efficiency and cost-effectiveness, making the process suitable for commercial production

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent prepares a defined medium composition with pre-optimized cytokine concentrations before differentiation begins, ensuring consistent and efficient differentiation from the start of the process

Inventive Principle:
Principle #10Preliminary action

Data Source

PatentUS9499790B2Method for promoting differentiation of pluripotent stem cells into cardiac muscle cells
Publication Date: 2016.11.22 KYOTO UNIV
  • US9499790B2 patent drawing
  • US9499790B2 patent drawing
  • US9499790B2 patent drawing

AI summary

The present invention relates to a composition for promoting differentiation of pluripotent stem cells into cardiac muscle cells, and a method for inducing differentiation of pluripotent stem cells into cardiac muscle cells and a method for preparing cardiac muscle cells.