Ex Vivo Immune Cell Reprogramming for Post-Infarct Fibrosis
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Solution Overview
Problem
Current therapies for myocardial infarction fail to effectively regenerate lost myocardial cells, leading to permanent cardiac dysfunction and ventricular remodeling, despite interventions that limit infarct size and improve microvascular circulation.
Innovation Solution
Ex vivo reprogramming of immune cells with regenerative cells, such as mesenchymal stem cells, to endow them with properties that inhibit cardiac fibrosis and promote myocardial regeneration, administered to patients post-myocardial infarction.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional therapies are used to limit infarct size and improve microvascular circulation, then infarct size is reduced and microvascular function is improved, but myocardial cell regeneration does not occur and permanent cardiac dysfunction persists
Solution Approach 1:
The patent uses immune cells as intermediaries that are reprogrammed by regenerative cells to mediate the regeneration process. The reprogrammed immune cells then act as mediators to promote myocardial cell regeneration and inhibit fibrosis in the infarcted tissue, bridging the gap between initial injury and functional recovery.
Solution Approach 2:
The patent changes the functional parameters of immune cells through ex vivo reprogramming with regenerative cells. This reprogramming alters the immune cells' properties to enable them to promote regeneration and inhibit fibrosis, transforming them from potentially harmful inflammatory agents into beneficial regenerative mediators.
2Reliability
If immune cells are activated immediately after myocardial infarction, then inflammatory response is initiated, but this leads to further myocardial damage and death
Solution Approach 1:
The patent applies preliminary action by reprogramming immune cells ex vivo before their administration to the infarcted heart. This pre-treatment modifies the immune cells' properties in advance, ensuring they will promote healing rather than cause damage when they reach the target tissue, thus preventing the harmful inflammatory response.
Solution Approach 2:
The patent converts the potentially harmful inflammatory immune cells into beneficial regenerative agents through ex vivo reprogramming. By exposing immune cells to regenerative cells before administration, the patent transforms their function from causing myocardial damage to promoting tissue regeneration and inhibiting fibrosis.
Data Source
AI summary
Disclosed are methods, means and compositions of matter useful for treatment of heart failure, and/or post infarct pathological remodeling using ex vivo reprogrammed immune cells. In one embodiment, cells of the recipient (autologous) are cocultured with a regenerative cell population alone or in the presence of one or more adjuvants. Said adjuvants enhance transfer of regenerative activity from said mesenchymal stem cells to said immune cells. In one embodiment said ex vivo reprogrammed immune cells are capable of inducing death or inactivation of cardiac fibrotic cells. In other embodiments, said immune cells provide antifibrotic activity to induce suppression of cardiac fibrosis. In other embodiments, said immune cells provide for growth factors to enhance cardiac regeneration.