MSC-EV Composition Stability via Serum-Free Media and Albumin
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Solution Overview
Problem
The clinical use of mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) is hindered by challenges in producing, storing, and handling them in a reliable and reproducible manner, necessitating the development of a composition with good stability and a commercially attractive shelf life for therapeutic applications.
Innovation Solution
A clinical-grade MSC-EV composition is developed, following Good Manufacturing Practice (GMP) guidelines, with specific production methods involving culturing MSCs in serum-free and xeno-free media, filtering, and concentrating the EVs to achieve high purity and stability, including the use of Annexin V and albumin for enhanced anti-inflammatory properties and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If MSCs are cultured in serum-containing media to produce EVs, then EV production yield is improved, but product purity and stability are worsened due to contamination with serum proteins and xenogeneic components
Solution Approach 1:
The patent changes the cultural parameters by using serum-free and xeno-free media formulations with specific growth factors and nutrients to maintain high EV production yield while eliminating serum protein contamination and xenogeneic components, achieving both high yield and high purity simultaneously
Solution Approach 2:
The patent employs disposable single-use bioreactors and culture systems that are pre-configured with serum-free media, eliminating the need for complex sterilization and media preparation steps while ensuring consistent purity across batches without requiring serum-containing media
2Adaptability or versatility
If EVs are produced without standardized GMP protocols, then production flexibility is improved, but batch-to-batch consistency and reliability are worsened
Solution Approach 1:
The patent segments the EV production process into distinct standardized modules including cell expansion, EV harvesting, purification, and formulation steps, each with defined parameters and quality controls that can be independently optimized while ensuring overall batch consistency through GMP compliance
Solution Approach 2:
The patent establishes standardized parameter ranges for critical process variables including cell density, media composition, harvest timing, and purification conditions, allowing flexibility within defined ranges while maintaining batch-to-batch consistency through controlled parameter specifications
3Device complexity
If EV compositions are formulated without stabilizing agents, then product simplicity is improved, but storage stability and shelf life are worsened
Solution Approach 1:
The patent introduces albumin as a stabilizing agent that acts as an intermediary between the EVs and the storage environment, protecting EVs from aggregation and degradation during storage and transport while maintaining product simplicity through the use of a single, well-characterized stabilizer at controlled concentrations
Data Source
AI summary
The current invention relates to a composition comprising extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs), said EVs are part of a population of particles in said composition having a particle size of between 0.05 and 0.22 micron, said concentration of these particles is at least 1×1011 particles per ml of composition and wherein at least 90% of said particles with particle size of between 0.05 and 0.22 micron are EVs, said EVs are defined by having a concentration of intra-vesicular Annexin V of at least 40 ng/ml and a concentration of extra-vesicular Annexin V of less than 1 ng/ml. The current invention also relates to the use such composition.