Pooled Allogeneic MSCs for Consistent COVID-19 Therapy
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Solution Overview
Problem
Current methods for using mesenchymal stem/stromal cells (MSCs) in treating COVID-19 face challenges such as batch-to-batch variability, difficulty in obtaining large batches with desired properties, and the risk of allosensitization, which complicates treatment efficacy and safety.
Innovation Solution
A method involving the selection and pooling of MSCs from multiple donors using a specific algorithm to create an isolated, pooled allogenic MSC population with controlled cell distribution and limited passages, ensuring low immunogenicity and consistent potency, which is administered without the need for donor-recipient matching.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If MSCs are expanded from multiple donors to obtain large batches, then cell quantity is improved, but batch-to-batch variability increases
Solution Approach 1:
The patent combines MSCs from multiple individual donors into a single pooled allogeneic population. This merging approach allows obtaining large cell batches suitable for clinical use while the pooling effect actually reduces batch-to-batch variability by creating a consistent, standardized cell product that can be manufactured in large quantities with uniform characteristics.
Solution Approach 2:
The patent changes the fundamental parameter of donor composition from single-donor to multi-donor pooled populations. By adjusting this parameter and establishing specific criteria for donor selection and cell pooling ratios, the invention achieves both large cell quantity and reduced variability, transforming the manufacturing consistency parameter through controlled parameter changes.
2Quantity of substance
If MSCs are pooled from multiple donors, then cell quantity and availability are improved, but immunogenicity and risk of allosensitization increase
Solution Approach 1:
The patent changes the immunogenicity parameter by controlling the number of passages the pooled cells undergo (limiting to no more than 10 passages) and by establishing specific donor selection criteria. This parameter control allows the pooled allogeneic population to maintain low immunogenicity despite comprising multiple donors, resolving the contradiction between cell availability and immunogenicity.
Solution Approach 2:
The patent performs preliminary selection and characterization of individual donor MSCs before pooling them into the final allogeneic population. By pre-screening donors and cells based on specific criteria (passage number, cell quality markers) before pooling, the invention prevents the accumulation of highly immunogenic cells, thereby reducing the risk of allosensitization while maintaining cell availability.
3Quantity of substance
If MSCs undergo extensive expansion to obtain sufficient cell numbers, then cell quantity is improved, but potency and genetic stability deteriorate
Solution Approach 1:
The patent merges cells from multiple donors at an earlier stage and performs a single coordinated expansion of the pooled population rather than extensive sequential expansion of individual donor cells. This approach achieves sufficient cell numbers for clinical use while limiting the total number of passages (to no more than 10), thereby preserving potency and genetic stability through reduced cumulative expansion stress.
Solution Approach 2:
The patent performs preliminary pooling of MSCs from multiple donors before conducting the expansion process. By establishing the pooled allogeneic population first and then expanding it in a controlled manner with limited passages, the invention achieves sufficient cell quantity while maintaining reliability, as the preliminary pooling structure prevents the need for excessive sequential expansions that would compromise potency and genetic stability.
Data Source
AI summary
The present disclosure relates to the use of allogeneic populations of mesenchymal stem/stromal cells and related compositions, which populations and compositions comprise cells pooled from multiple donors, in the treatment and/or prevention of COVID-19 infection or for use in the treatment and/or prevention of symptoms associated with COVID-19 infection. The present disclosure also relates to methods for obtaining said compositions.