APP-Derived Synthetic Peptide for Endodermal Differentiation

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Solution Overview

Problem

Current methods for inducing differentiation of pluripotent stem cells into endodermal cells are inefficient, often requiring complex operations, multiple exogenous genes, or costly cytokines, with low differentiation efficiency and safety concerns, and the resulting cells may not function satisfactorily.

Innovation Solution

A synthetic peptide derived from amyloid precursor protein (APP) or its related proteins, specifically designed to induce differentiation of pluripotent stem cells into endodermal cells, which is easy to manufacture and administer, eliminating the need for expensive cytokines and avoiding genetic modification.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional methods are used to induce differentiation of pluripotent stem cells into endodermal cells, then differentiation can be achieved, but the process requires complex operations, multiple exogenous genes, or costly cytokines with low differentiation efficiency

Engineering Contradiction:
Improvedifferentiation efficiencyVSAvoidoperation complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The invention extracts and utilizes the natural differentiation-inducing capability already present in the pluripotent stem cells themselves, rather than introducing external complex factors. By removing the need for exogenous genes and costly cytokines, the method achieves high differentiation efficiency through a simple, elegant approach that leverages the cell's intrinsic properties

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention replaces expensive, complex differentiation-inducing factors with a simple, cost-effective method that uses basic culture conditions. This disposable-like approach eliminates the need for continuous supply of costly cytokines and complex gene manipulation materials, making the process economically viable and easily repeatable

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

2Reliability

If exogenous genes are introduced to induce differentiation, then differentiation can be achieved, but safety issues arise due to genome DNA incorporation

Engineering Contradiction:
Improvedifferentiation reliabilityVSAvoidsafety concerns
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention converts the potential harm of genetic manipulation into a benefit by completely avoiding it. Instead of introducing exogenous genes that could cause safety issues, the method uses the cell's natural differentiation pathways, turning the absence of genetic intervention into a safety advantage while maintaining reliable differentiation outcomes

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The pluripotent stem cells are enabled to perform their own differentiation function without external genetic intervention. The cells' inherent biological programs are activated through simple culture conditions, allowing them to self-differentiate into endodermal cells safely and reliably without incorporating foreign DNA

Inventive Principle:
Principle #25Self-service

3Productivity

If multiple kinds of differentiation-inducing compounds are added to medium, then differentiation can be achieved, but cost increases due to large quantities of expensive cytokines required

Engineering Contradiction:
Improvedifferentiation efficiencyVSAvoidcost
Core Design Contradiction:
ProductivityVSQuantity of substance

Solution Approach 1:

The invention extracts and eliminates the need for expensive cytokines and differentiation-inducing compounds from the culture system. By removing these costly substances and relying on the cells' natural differentiation capacity, the method achieves high efficiency while dramatically reducing material costs

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention replaces expensive, continuously required cytokines with a simple, cost-effective culture approach. The basic culture medium serves as a disposable, low-cost alternative to expensive growth factors, enabling repeated experiments and large-scale production without prohibitive material costs

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

4Productivity

If conventional differentiation induction methods are used, then endodermal cells can be produced, but the resulting cells often do not function satisfactorily

Engineering Contradiction:
Improvecell production quantityVSAvoidcell function quality
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The pluripotent stem cells are enabled to perform their own differentiation function without external genetic intervention. The cells' inherent biological programs are activated through simple culture conditions, allowing them to self-differentiate into endodermal cells safely and reliably

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

Instead of forcing differentiation through external factors that may produce dysfunctional cells, the invention inverts the approach by removing inhibitory factors and allowing natural differentiation to occur. This reversal of the conventional forcing approach results in cells that maintain proper function while differentiating

Inventive Principle:
Principle #13The other way round (Inversion)

Data Source

PatentEP3088415B1Method for inducing differentiation of pluripotent stem cells into endodermal cells
Publication Date: 2019.11.06 TOAGOSEI CO LTD
  • EP3088415B1 patent drawingFigure 1
  • EP3088415B1 patent drawingFigure 2
  • EP3088415B1 patent drawingFigure 3

AI summary

Provided are a synthetic peptide having a stem cell differentiation-inducing activity to induce differentiation of pluripotent stem cells into endodermal cells, a stem cell differentiation inducer having this peptide as an active ingredient, and a method for inducing differentiation of pluripotent stem cells using these. The synthetic peptide provided by the present invention contains a stem cell differentiation-inducing peptide sequence, and this stem cell differentiation-inducing peptide sequence is selected from an amino acid sequence constituting a signal peptide in any of amyloid precursor proteins (APP), amyloid precursor-like protein (APLP) 1 and APLP2, which are known as proteins belonging to the APP family, a partial amino acid sequence an amino acid sequence constituting this signal peptide, or a modified amino acid sequence formed by substitution, deletion and/or addition of 1, 2 or 3 amino acid residues in these amino acid sequences.