Gene Modified iPSC Derived Cellular Compositions for Regeneration
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Solution Overview
Problem
Current stem cell therapies lack reproducibility and effectiveness in phase III trials, except for graft versus host disease, and there is a need for more potent stem cell therapeutics that can induce tissue repair and immune modulation for degenerative conditions affecting various organ systems.
Innovation Solution
Methods involving the generation of pluripotent stem cells, their differentiation into regenerative cells with chemoattractant and immune modulatory activities, using proteins like OCT4, NANOG, and SOX2, and gene modification to create mesenchymal stem cells capable of tissue-specific differentiation and immune modulation, such as through the introduction of IL-27 for anti-inflammatory effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional stem cell therapy is used, then treatment is provided for degenerative conditions, but the therapy lacks reproducibility and effectiveness in phase III trials
Solution Approach 1:
The patent modifies stem cells by introducing specific genes (CXCL12, IL-27, HGF) to change their functional parameters. This genetic modification transforms conventional stem cells into enhanced therapeutics with improved reproducibility and effectiveness, directly addressing the reliability issue in phase III trials while maintaining treatment productivity
Solution Approach 2:
The patent creates composite cellular therapies by combining stem cells with specific gene modifications and multiple functional components (chemoattractant activity, immune modulatory activity, tissue repair capability). This composite approach produces a more potent and reliable therapeutic that overcomes the limitations of conventional single-function stem cell therapies
2Strength
If stem cells are modified to enhance regenerative function, then tissue repair capability is improved, but immune modulation capability may be compromised
Solution Approach 1:
The patent merges multiple therapeutic functions into a single modified stem cell by co-introducing genes for chemoattractant activity (CXCL12), immune modulatory activity (IL-27), and tissue repair (HGF). This combining approach ensures that enhancing tissue repair capability does not compromise immune modulation, as both functions are integrated into the same cellular platform
Solution Approach 2:
The patent creates multi-functional stem cells that simultaneously perform tissue repair, immune modulation, and cell recruitment. This universal approach allows a single therapeutic to address multiple aspects of degenerative conditions, ensuring that improvements in one function do not come at the expense of others
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
The approach enables the development of stem cell therapeutics that can effectively treat degenerative conditions by promoting tissue repair and immune modulation across multiple organ systems, enhancing regenerative and immune functions.
Implementation Method 1
dedifferentiation is accomplished by introduction into cells proteins capable of inducing dedifferentiation
Implementation Method 2
said MSC are differentiated by exposure to BMP-2
Implementation Method 3
said MSC are transfected with IL-27 to induce anti-inflammatory effects
Data Source
AI summary
Disclosed are cells and cellular compositions useful for treatment of degenerative and/or autoimmune diseases derived from gene edited/gene modified pluripotent stem cells. In one embodiment pluripotent stem cell such as inducible pluripotent stem cells are gene modified to express tissue associated transcription factors such as pdx-1 if endodermal tissue is desired and cells are differentiated into regenerative-type cells such as along the mesenchymal lineage. In one embodiment the invention teaches transfection with IL-27 to induce expression of coinhibitory molecules for suppression of autoimmunity. In some embodiments the invention provides generation of iPSC derived MSC which can not stimulate inflammation due to gene-editing based removal of inflammatory associated transcription factors.