Altered Adherent Stromal Cells Cytokine Priming Bioreactor Growth
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Solution Overview
Problem
Current methods for cytokine treatment of placental-derived adherent stromal cells (ASC) are limited, particularly in developing effective methods for exponential growth in bioreactors and understanding the effects of ex-vivo cytokine treatment, which hinders the production of therapeutic factors and their therapeutic applications.
Innovation Solution
ASC are expanded in media with inflammatory cytokines, using a two-step process where the first step occurs without added cytokines and the second step is performed in their presence, resulting in cells that exhibit unique characteristics and produce elevated therapeutic factors, suitable for systemic or distant tissue administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If placental ASC are expanded in medium containing inflammatory cytokines, then the cells produce elevated amounts of therapeutic factors, but the understanding of ex-vivo cytokine treatment effects is limited and methods for exponential growth in bioreactors are not yet developed
Solution Approach 1:
The patent applies preliminary action by first expanding placental ASC in medium without inflammatory cytokines to achieve exponential growth and establish a robust cell population, then subsequently introducing inflammatory cytokines to prime the cells for enhanced therapeutic factor production. This sequential approach ensures cells are adequately expanded before subjecting them to cytokine treatment, resolving the contradiction between achieving exponential growth and producing therapeutic factors.
Solution Approach 2:
The expansion process is segmented into two distinct phases: Phase 1 involves expanding placental ASC in cytokine-free medium to achieve exponential growth, while Phase 2 involves introducing inflammatory cytokines to prime cells for therapeutic factor production. This segmentation allows each phase to optimize for its specific goal without interference, thereby resolving the technical contradiction between productivity and therapeutic factor quantity.
2Quantity of substance
If a two-step process is used with first step without cytokines and second step with inflammatory cytokines, then cells exhibit unique characteristics and produce elevated therapeutic factors, but the process complexity increases
Solution Approach 1:
The two-step process is segmented into distinct phases with clear objectives: Step 1 focuses on cell expansion without cytokines, while Step 2 introduces inflammatory cytokines for therapeutic factor production. Each step is optimized independently, allowing straightforward implementation despite the increased number of steps. The segmentation makes the process manageable and reproducible, offsetting the complexity with clear procedural definition.
Solution Approach 2:
The process utilizes parameter changes by transitioning from a cytokine-free environment in Step 1 to an inflammatory cytokine-containing environment in Step 2. This controlled change in medium composition triggers the desired cellular response and therapeutic factor production. The parameter change approach provides a simple yet effective mechanism to achieve unique cell characteristics without requiring complex device modifications.
3Adaptability or versatility
If placental ASC are treated with inflammatory cytokines, then they are primed to produce elevated therapeutic factors suitable for systemic administration, but the effects of ex-vivo cytokine treatment are not yet fully understood
Solution Approach 1:
The patent applies preliminary action by using inflammatory cytokines to prime placental ASC in advance, which enhances their therapeutic factor production capacity and prepares them for systemic administration. This priming step ensures cells are pre-conditioned to exert therapeutic effects at distant sites without requiring long-term engraftment, thereby improving adaptability while building reliability through controlled ex-vivo treatment.
Solution Approach 2:
Inflammatory cytokines serve as intermediaries that mediate the transformation of placental ASC into therapeutically enhanced cells. These cytokines temporarily modify cell behavior and function during the expansion process, enabling the cells to produce elevated therapeutic factors. The intermediary作用 allows controlled modification of cell properties without permanent genetic alteration, enhancing both adaptability and reliability of the treatment approach.
Data Source
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AI summary
Disclosed herein are altered adherent stromal cells and methods of producing and utilizing same.