Cardiogenic Mesoderm Regulators for Progenitor Cell Generation

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Solution Overview

Problem

Current knowledge on cardiogenic mesoderm formation is fragmented, lacking comprehensive understanding of intracellular mediators, which hinders the development of regenerative and disease modeling technologies for cardiac disorders.

Innovation Solution

Overexpression of proteins such as Id1, Id2, Id3, Id4, Evx1, and Grrp1 in stem cells, or inhibition of Foxa2 and Tcf3, to generate multipotent cardiovascular progenitor cells, promoting cardiogenic mesoderm formation and cardiac regeneration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of information

If comprehensive approaches are used to identify cardiogenic mesoderm formation regulators, then understanding of intracellular mediators is improved, but research time and resources are increased

Engineering Contradiction:

Improveknowledge completenessVSAvoidresearch duration

Core Design Contradiction:

Loss of informationVSLoss of time

Solution Approach 1:

The patent performs preliminary identification and validation of key intracellular mediators (Id1, Evx1, Grrp1) before using them in systematic screening approaches. This preliminary characterization enables subsequent high-throughput studies to proceed efficiently without repeating basic validation experiments, thus resolving the contradiction between comprehensive knowledge acquisition and research time investment

Inventive Principle:

Principle #10Preliminary action

2Productivity

If multiple proteins are overexpressed to generate multipotent cardiovascular progenitor cells, then cell generation efficiency is improved, but process complexity is increased

Engineering Contradiction:

Improveprogenitor cell generationVSAvoidtransfection process

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The patent combines multiple overexpression strategies (Id1, Evx1, Grrp1) into a unified transfection protocol using lentiviral vectors. By merging these molecular approaches into a single integrated process, the patent achieves high productivity in generating multipotent cardiovascular progenitor cells while managing process complexity through standardization

Inventive Principle:

Principle #5Merging (Combining)

3Reliability

If stem cells are differentiated into multipotent cardiovascular progenitor cells, then regenerative potential is improved, but differentiation control difficulty is increased

Engineering Contradiction:

Improveregenerative capabilityVSAvoiddifferentiation control

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent systematically modifies differentiation parameters including transcription factor expression levels (Id1, Evx1, Grrp1), signaling pathway activation (Activin, BMP, Wnt), and temporal exposure durations. By establishing quantitative relationships between these parameters and differentiation outcomes, the patent improves regenerative reliability while making differentiation control more predictable and manageable

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS11821003B2Cardiogenic mesoderm formation regulators

Publication Date: 2023.11.21 SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INST

AI summary

This disclosure relates to cardiogenic mesoderm formation regulators and methods of use thereof, e.g., generating a multipotent cardiovascular progenitor cell by overexpressing Id1, Id2, Id3, Id4, Evx1, and/or Grrp1 in a stem cell.