Reprogramming Somatic Cells to Corneal Endothelial Cells

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Solution Overview

Problem

Corneal endothelial cells have limited capacity for proliferation, leading to cell loss with age, resulting in decreased cell density and compromised corneal function, causing corneal clouding, stromal edema, and potential blindness, with existing therapeutic methods being insufficient for effective reconstruction.

Innovation Solution

A method for reprogramming somatic cells into corneal endothelial cell-like cells using specific combinations of reprogramming factors such as GSK3 inhibitors, TGFβ inhibitors, cyclic AMP inducers, and casein kinase 1 inhibitors, allowing for the conversion of cells into functional corneal endothelial cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If corneal endothelial cells are used to maintain corneal function, then corneal transparency and fluid balance are preserved, but cell density decreases with age leading to compromised function

Engineering Contradiction:
Improvecorneal functionVSAvoidcell density
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

The patent applies parameter changes by using chemical reprogramming factors (GSK3 inhibitors, TGFβ inhibitors, cyclic AMP inducers, and casein kinase 1 inhibitors) to alter the cellular state and differentiation potential of somatic cells, enabling them to become functional corneal endothelial cell-like cells that can restore and maintain corneal function

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates corneal endothelial cell-like cells through reprogramming somatic cells to replicate the functional characteristics of native corneal endothelial cells, providing a renewable source that can restore corneal transparency and fluid balance without depleting the original cell population

Inventive Principle:
Principle #26Copying

2Stability of the object's composition

If corneal endothelial cells do not proliferate in vivo, then natural replacement is prevented, but cell loss occurs with age requiring therapeutic intervention

Engineering Contradiction:
Improvecell population stabilityVSAvoidcell number
Core Design Contradiction:
Stability of the object's compositionVSQuantity of substance

Solution Approach 1:

The reprogrammed corneal endothelial cell-like cells possess the ability to self-renew and proliferate in culture, providing a self-sustaining cell population that can be expanded and used for therapeutic purposes to replace age-related cell loss in the cornea

Inventive Principle:
Principle #25Self-service

3Reliability

If existing therapeutic methods are used for corneal reconstruction, then some treatment effect is achieved, but significant need for novel reconstruction methods remains

Engineering Contradiction:
Improvetherapeutic effectVSAvoidreconstruction capability
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent employs chemical reprogramming factors to fundamentally change the differentiation state and functional properties of somatic cells, enabling them to become corneal endothelial cell-like cells with the specific functional characteristics needed for effective corneal reconstruction and regeneration

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentUS20230416676A1Method for Reprogramming Cell
Publication Date: 2023.12.28 MOUCELLION THERAPEUTICS LTD
  • US20230416676A1 patent drawing
  • US20230416676A1 patent drawing
  • US20230416676A1 patent drawing

AI summary

Provided are a method for reprogramming a cell in the presence of one or more reprogramming factors, a reprogrammed cell obtained by using the method and use thereof, and a kit comprising the reprogramming factors.