Myoblast Chimeric Cell Fusion for Muscular Dystrophy Therapy
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Solution Overview
Problem
There is no known cure for muscular dystrophies such as Becker's and Duchenne's muscular dystrophy, and existing treatments focus on symptom management rather than addressing the underlying muscle degeneration.
Innovation Solution
The generation and use of myoblast chimeric cells (MCCs) composed of myoblasts from a patient with muscle disease and a healthy donor, created through cell fusion methods involving polyethylene glycol and controlled passaging, to treat muscular dystrophy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If cell fusion methods are used to generate MCCs, then therapeutic potential for muscle disease is improved, but process complexity and manufacturing precision requirements increase
Solution Approach 1:
The patent optimizes specific parameters including polyethylene glycol concentration (1.0-1.3 g/ml), passaging次数 (2-5 times), and confluency (60-80%) to control cell fusion efficiency and MCC quality, transforming an unpredictable biological process into a controllable manufacturing process
Solution Approach 2:
The patent implements quality control through CD marker expression testing (CD56>50-70%, CD90>50-70%, CD34<5-10%, CD45<5-10%) at various stages to ensure MCC purity and therapeutic quality, using feedback from marker analysis to adjust processing parameters
2Quantity of substance
If multiple passaging is performed to expand myoblast cultures, then cell quantity is improved, but cell quality and purity deteriorate
Solution Approach 1:
The patent performs a controlled number of passaging (2-5 times) - not too few to limit cell quantity, not too many to compromise quality - optimizing the balance between expansion and quality maintenance
Solution Approach 2:
CD marker expression levels are monitored during passaging to detect quality changes, with specific thresholds (CD56>50%, CD90>50%, CD34<10%, CD45<10%) providing feedback to determine when to stop passaging and proceed to fusion
3Productivity
If polyethylene glycol concentration is increased to enhance cell fusion, then fusion efficiency is improved, but cell damage and harmful effects increase
Solution Approach 1:
The patent optimizes polyethylene glycol concentration to 1.0-1.3 g/ml, a specific range that provides sufficient fusion efficiency while minimizing cell damage, and controls exposure time to further reduce harmful effects
Solution Approach 2:
Polyethylene glycol acts as a temporary intermediary that facilitates membrane fusion but is removed afterward, allowing the beneficial fusion effect while eliminating the harmful substance from the final MCC product
4Adaptability or versatility
If cell fusion is performed to create chimeric cells, then therapeutic versatility is improved, but process complexity increases
Solution Approach 1:
The patent combines patient-specific myoblasts (providing disease-relevant genetic background) with donor myoblasts (providing healthy functional genes) into chimeric MCCs, merging the advantages of both cell sources for targeted therapy
Solution Approach 2:
The patent divides the treatment approach into distinct segments: patient myoblast isolation, donor myoblast preparation, controlled fusion, quality control, and targeted delivery, making the complex process manageable and scalable
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
MCCs potentially offer a therapeutic approach to slow down muscle degeneration and improve muscle function, with specific markers like CD56 and CD90 expression ensuring cell quality, enabling intra-bone delivery for targeted treatment.
Implementation Method 1
cell fusion methods are performed using 2-4 times, or 5 times, passaged myoblasts from the MD and donor subject, and/or polyethylene glycol at 1.0-1.3 g/ml or 0.4-1.5 g/ml (e.g., about 0.65 g/ml)
Data Source
AI summary
The present invention relates to methods and compositions for generating and using myoblast chimeric cells (MCCs) for treating a muscle disease, such as muscular dystrophy, where the MCCs are composed of a myoblast derived from a patient with muscle disease (MD) and a myoblast from a donor without the MD (e.g., a healthy donor). In certain embodiments, cell fusion methods are performed using 2-4, or 5, times passaged myoblasts from the MD and donor subject, and/or polyethylene glycol 0.5-1.5 g/ml. In other embodiments, the MCCs created by fusion are passaged 1-5 times before use, and are passaged at 60-80% confluency. In further embodiments, the myoblasts and/or MCCs are tested at any stage during the process for less than 5-10% CD34 and/or CD45 expression, and/or greater than 50-70% CD56 and/or CD90 expression.