Ex Vivo Reprogrammed Immune Cells for Renal Failure
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Solution Overview
Problem
Current treatments for kidney failure, including chronic and acute forms, are inadequate in preventing or reversing renal damage and fibrosis, particularly in cases induced by ischemia/reperfusion injury, chemotherapy, and autoimmune-mediated conditions.
Innovation Solution
The method involves identifying patients with renal failure, extracting immune cells, contacting them with regenerative cells to impart inhibitory properties, and administering these modified immune cells back into the patient to prevent or reverse renal failure, using techniques such as culturing with activators like Pam3CSK4, Poly:IC, and LPS to activate specific immune receptors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional treatments for kidney failure are used, then current standard care is provided, but renal damage and fibrosis are not effectively prevented or reversed
Solution Approach 1:
The patent uses regenerative cells as intermediary agents that transfer reprogramming factors to immune cells. These regenerative cells act as mediators between the patient's immune system and the desired therapeutic outcome, enabling the immune cells to acquire pro-regenerative properties without direct manipulation of the kidney tissue itself.
Solution Approach 2:
The patent changes the functional parameters of immune cells by contacting them with regenerative cells in vitro. This reprogramming process alters the expression profile and functional characteristics of the immune cells, transforming them from their original state to a pro-regenerative state that can inhibit fibrosis and promote tissue repair when administered back to the patient.
2Reliability
If immune cells are extracted and modified in vitro, then therapeutic properties are enhanced, but the process complexity increases
Solution Approach 1:
The regenerative cells perform the reprogramming function through direct cell-to-cell contact with the immune cells in culture. The regenerative cells utilize their inherent regenerative properties and secreted factors to automatically transfer reprogramming signals, eliminating the need for complex external reprogramming systems or direct genetic manipulation.
Solution Approach 2:
The regenerative cells serve as a natural intermediary that simplifies the reprogramming process. Instead of requiring complex in vitro reprogramming protocols, the regenerative cells mediate the transfer of therapeutic properties through their contact with immune cells, reducing the overall system complexity while maintaining therapeutic efficacy.
3Reliability
If reprogrammed immune cells are administered to reverse renal failure, then therapeutic reversal is achieved, but the risk of immune response and tissue damage increases
Solution Approach 1:
The immune cells are reprogrammed to recognize and respond to renal damage signals in a regulated manner. The reprogramming process equips the immune cells with the ability to selectively target damaged tissue while sparing healthy tissue, using the patient's own damage signals as guidance for therapeutic action.
Solution Approach 2:
The reprogrammed immune cells exhibit local quality by responding specifically to the chemical and physical signals present at the site of renal damage. This localized response ensures that the therapeutic effect is concentrated at the site of injury rather than causing widespread immune activity, thereby reducing the risk of immune-mediated damage to healthy tissue.
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
This approach effectively inhibits and reverses renal failure by enhancing the immune system's ability to address renal damage, fibrosis, and ischemia/reperfusion injury, offering a prophylactic and therapeutic solution for various kidney disease scenarios.
Implementation Method 1
contacting said immune cells with regenerative cells in a manner so that regenerative cells endow onto said immune cells properties capable of inhibiting and/or reversing renal failure and/or renal fibrosis
Implementation Method 2
using techniques such as culturing with activators like Pam3CSK4, Poly:IC, and LPS to activate specific immune receivers
Data Source
AI summary
Disclosed are treatment methods, protocols, and compositions of matter useful for treatment of kidney failure. The invention discloses, in one embodiment, administration of immune cells that have been reprogrammed by co-culture with regenerative cells. In one embodiment said regenerative cells are umbilical cord derived mesenchymal stem cells and said immune cells are peripheral blood mononuclear cells. In one embodiment cells are cultured together in the presence of interleukin 2 and/or an mTOR inhibitor. In one embodiment said cells are cultured together in the presence of an anti-CD3 and/or anti-CD28 antibody.