Immortalized Human Mast Cell Line for Allergy Screening
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Solution Overview
Problem
Current methods for obtaining pure populations of human mast cells are inefficient, expensive, and variable, making it difficult to study IgE-dependent activation and develop therapeutic strategies for allergic and mastocytosis-related conditions, as existing cell models lack reproducibility and specificity for targeting KIT mutations like D816V.
Innovation Solution
Development of a human mast cell line, ROSA KIT WT, expressing wild-type KIT and high-affinity IgE receptors, with stable morphological and functional characteristics, allowing for high-throughput screening and easy manipulation, and derivation of mutant lines like ROSA KIT D816V and ROSA KIT Delta 417-419 insY to model pathological conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If current methods are used to obtain pure populations of human mast cells, then some mast cells can be obtained, but the process is inefficient, expensive, and variable with poor reproducibility
Solution Approach 1:
The patent creates a cell line (HMC-1) that copies the essential characteristics of primary human mast cells, including morphology, ultrastructure, phenotype, and IgE-dependent activation capability. This immortalized line serves as a reproducible model that eliminates the variability inherent in primary cell isolation methods while maintaining biological relevance for studying mast cell function and allergic responses.
Solution Approach 2:
The patent modifies cellular parameters by establishing an immortalized cell line with specific characteristics: stable expression of mast cell markers (tryptase, chymase, CD117, FcεR1), defined morphology with metachromatic granules, and controlled proliferation rates. These parameter changes create a standardized model that is both reproducible and biologically relevant.
2Adaptability or versatility
If existing cell models are used, then some research can be conducted, but they lack specificity for targeting KIT mutations like D816V found in mastocytosis
Solution Approach 1:
The patent segments the research application by creating specialized sublines from the parent HMC-1 cell line. The HMC-1.2 subline specifically models the KIT D816V mutation found in mastocytosis, while the parent line models wild-type KIT. This segmentation allows researchers to select the appropriate model for their specific research question, enhancing adaptability without requiring derivation of entirely new cell lines.
Solution Approach 2:
The HMC-1 cell line serves multiple functions: it can model both wild-type KIT (parent line) and KIT D816V mutation (HMC-1.2 subline), study IgE-dependent activation, investigate allergic responses, and explore mastocytosis pathogenesis. This multi-functionality reduces the need for multiple specialized cell lines while maintaining research versatility.
3Reliability
If primary mast cells are isolated from tissues, then authentic human mast cells can be obtained, but the yield is low (maximum 1-3 million cells) and the process is expensive and detrimental to cell functionality
Solution Approach 1:
The patent performs preliminary action by establishing an immortalized cell line that can be propagated indefinitely in vitro. This eliminates the need for repeated isolation from primary tissues, ensuring authentic human mast cell characteristics are maintained while providing unlimited cellular yield for research purposes.
Solution Approach 2:
The HMC-1 cell line is self-sufficient, producing unlimited quantities of authentic human mast cells through continuous in vitro proliferation. The cells maintain their functional characteristics (IgE receptor expression, degranulation capability, cytokine production) while serving their own propagation needs, eliminating dependence on primary tissue sources.
Data Source
AI summary
The present invention relates to a human mast cell line corresponding to deposit number CNCM I-4551 and also to the lines derived therefrom, in particular the derived lines corresponding respectively to deposit numbers CNCM I-4552 and CNCM I-4553, and to the uses thereof, in particular for screening for compounds of therapeutic interest.