Cardiac Neural Crest Cell Differentiation via cKit Purification

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Solution Overview

Problem

Current methods lack effective and reliable ways to identify and utilize cardiac neural crest cells for treating cardiac injuries, such as myocardial infarction and cardiomyopathy, due to uncertainties in their role and availability from adult mammals, as well as the lack of specific cell-surface markers for immunological identification and purification.

Innovation Solution

A method involving the use of cKit positive cardiac neural crest cells, which are cultured with noggin and leukemia inhibitory factor to form three-dimensional aggregates, and then differentiated into cardiac neural crest cells using a specific medium, with the option of adding differentiation agents like BMP antagonists and retinoic acid to enhance their therapeutic potential.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If stem cells are used to treat cardiac injuries, then therapeutic potential is improved, but reliability is worsened due to uncertainties in cell identification and availability

Engineering Contradiction:

Improvereliability of cardiac injury treatmentVSAvoiddifficulty of identifying and purifying cardiac neural crest cells

Core Design Contradiction:

ReliabilityVSDifficulty of detecting and measuring

Solution Approach 1:

The patent uses cKit as a cell-surface marker to identify and purify cardiac neural crest cells. This marker enables reliable detection and isolation of the specific cell population needed for cardiac injury treatment, resolving the contradiction between therapeutic potential and identification difficulty.

Inventive Principle:

Principle #32Color changes

Solution Approach 2:

The patent employs immunological methods using cKit antibodies as intermediaries to purify cardiac neural crest cells from mixed cell populations. This intermediary approach enables reliable cell separation and identification, addressing the reliability improvement while overcoming the detection difficulty.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If cardiac neural crest cells are cultured and differentiated, then therapeutic effectiveness is improved, but device complexity is worsened due to multiple culture steps and differentiation agents

Engineering Contradiction:

Improvetherapeutic effectiveness for cardiac regenerationVSAvoidcomplexity of cell culture and differentiation process

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent performs preliminary culturing of cardiac neural crest cells with noggin and leukemia inhibitory factor to form three-dimensional aggregates before differentiation. This preliminary action prepares the cells in advance, improving their therapeutic effectiveness while organizing the complex process into manageable sequential steps.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent uses differentiation agents such as BMP antagonists and retinoic acid to change the cultural parameters and induce cardiac neural crest cell differentiation. By controlling these chemical parameters, the patent achieves reliable cell differentiation for cardiac regeneration while managing the complexity through defined parameter adjustments.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS10786536B2Cardiac neural crest cells and methods of use thereof

Publication Date: 2020.09.29 VESTION

AI summary

Cardiac neural crest cells and methods for making and using the same to effect cardiac injury is described herein.