AV Node-Like Pacemaker Cells for Biological Conduction Bridging

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Solution Overview

Problem

Current methods for treating atrioventricular node (AVN) block, such as electronic pacemaker implantation, have high complication rates and lack autonomic responsiveness, and there is a need for a biological conduction bridge that can propagate electrical impulses like the AVN.

Innovation Solution

Methods for generating cardiomyocytes enriched for atrioventricular node-like pacemaker cells (AVNLPCs) by culturing human cardiac progenitors in a medium comprising Wnt agonists or bone morphogenetic proteins (BMPs) to produce AVNLPCs, characterized by NKX2-5+TBX3+ expression.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If electronic pacemaker implantation is used to treat AVN block, then the heart rhythm can be controlled, but the complication rate increases and autonomic responsiveness is lost

Engineering Contradiction:

Improveheart rhythm controlVSAvoidcomplication rate

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses human pluripotent stem cells differentiated into atrioventricular node-like pacemaker cells that copy the functional properties of natural AVN cells, including autonomic responsiveness and rhythmic contraction coordination, replacing electronic pacemakers with a biological tissue graft

Inventive Principle:

Principle #26Copying

Solution Approach 2:

The patent replaces the electronic pacemaker system with a biological tissue-based pacemaker using stem cell-derived cardiomyocytes that naturally generate and propagate electrical impulses, eliminating the need for electronic components and leads

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Reliability

If electronic pacemaker implantation is used to treat AVN block, then the heart rhythm can be controlled, but the device complexity increases

Engineering Contradiction:

Improveheart rhythm controlVSAvoidpacemaker system complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent creates a simplified system by using stem cell-derived pacemaker cells that inherently possess the complexity of natural AVN function, eliminating the need for external electronic control systems, batteries, and leads

Inventive Principle:

Principle #26Copying

Solution Approach 2:

The stem cell-derived pacemaker cells autonomously generate electrical impulses and respond to physiological conditions without external control, similar to natural pacemaker cells, thereby reducing system complexity

Inventive Principle:

Principle #25Self-service

3Adaptability or versatility

If human pluripotent stem cells are differentiated into AVN-like pacemaker cells, then a biological conduction bridge can be created, but the manufacturing precision must be high to ensure proper cell phenotype and function

Engineering Contradiction:

Improvebiological conduction bridgeVSAvoidcell phenotype control

Core Design Contradiction:

Adaptability or versatilityVSManufacturing precision

Solution Approach 1:

The patent employs specific culture conditions including Wnt agonists (CHIR-99021), bone morphogenetic proteins (BMP2, BMP4), and activin A at defined concentrations and durations to precisely control the differentiation trajectory and achieve the desired AVN-like phenotype

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The differentiation protocol uses sequential media changes and timing controls to monitor and adjust the cell development stages, ensuring proper phenotypic expression and functional maturation of the pacemaker cells

Inventive Principle:

Principle #23Feedback

Data Source

PatentUS20260022340A1Atrioventricular node-like pacemaker cells

Publication Date: 2026.01.22 UNIV HEALTH NETWORK

AI summary

The present disclosure provides methods of generating atrioventricular node like pacemaker cells in tissue culture and methods of using these cells.