Tie2-Expressing Monocytes for Angiogenesis Regulation

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Solution Overview

Problem

Current treatments for disorders associated with excessive angiogenesis or insufficient blood vessel growth are inadequate, and there is a need for methods to monitor angiogenesis in patients undergoing treatment.

Innovation Solution

Identification and characterization of human Tie2-expressing monocytes (TEMs) with distinct surface markers, which can promote or inhibit angiogenesis, and their use in therapies, diagnostics, and gene delivery for regulating angiogenesis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional angiogenesis therapies are used, then blood vessel growth is stimulated, but treatment effectiveness is insufficient and lacks targeted monitoring

Engineering Contradiction:
Improvetreatment effectivenessVSAvoidtherapy complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent uses Tie2-expressing monocytes as intermediary cells that naturally target sites of angiogenesis. These monocytes serve as living vectors that deliver therapeutic genes specifically to areas needing treatment, eliminating the need for complex external delivery systems while improving treatment reliability through targeted action

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent employs the body's own Tie2-expressing monocytes to perform the therapeutic function. By genetically modifying these endogenous cells, they autonomously navigate to angiogenic sites and deliver treatment, eliminating the need for complex external delivery mechanisms and enabling self-directed targeted therapy

Inventive Principle:
Principle #25Self-service

2Measurement precision

If angiogenesis is monitored in patients, then treatment monitoring capability is improved, but diagnostic complexity increases

Engineering Contradiction:
Improveangiogenesis monitoring accuracyVSAvoiddiagnostic complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent uses luciferase reporter genes that produce bioluminescent signals in Tie2-expressing monocytes. This allows non-invasive optical monitoring of angiogenesis in real-time through simple imaging, providing precise measurement without complex diagnostic equipment

Inventive Principle:
Principle #32Color changes

Solution Approach 2:

The patent incorporates reporter genes that provide real-time feedback on angiogenesis activity and gene delivery effectiveness. This continuous monitoring capability allows treatment optimization based on actual biological responses, improving measurement precision through simple readout mechanisms

Inventive Principle:
Principle #23Feedback

3Adaptability or versatility

If Tie2-expressing monocytes are used for targeted therapy, then treatment specificity is improved, but cell isolation and characterization complexity increases

Engineering Contradiction:
Improvetreatment targeting capabilityVSAvoidcell isolation complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent uses Tie2 as a natural intermediary marker that specifically identifies monocytes involved in angiogenesis. This endogenous marker eliminates the need for complex exogenous labeling systems while providing high treatment specificity through natural biological targeting

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent exploits the specific surface marker expression profile of Tie2-expressing monocytes (CD14+, CD16+, Tie2+) as a parameter change that enables their identification and isolation. This natural phenotypic distinction simplifies cell sorting compared to creating artificial markers, reducing isolation complexity while maintaining high targeting capability

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentUS7833789B2Monocyte cell
Publication Date: 2010.11.16 FOND AZIONE TELETHON
  • US7833789B2 patent drawing
  • US7833789B2 patent drawing
  • US7833789B2 patent drawing

AI summary

The present invention relates to human and mouse monocyte cells expressing Tie2 and CD14 or CD16 and their use in methods for regulating angiogenesis and vascular integrity, such as methods of inducing angiogenesis, promoting vessel growth or stabilization, treating pathological disorders, inhibiting angiogenesis, and diagnosing or monitoring a pathological disorder.