Regenerative T Cells from Pluripotent Stem Cells
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Solution Overview
Problem
Current stem cell therapy is limited by pulmonary blockade of intravenously injected mesenchymal cells due to their large size and donor-to-donor variability, leading to inconsistent clinical results despite identical visual and phenotypic characteristics.
Innovation Solution
The development of 'universal donor' regenerative T cells from standardized and activated pluripotent stem cells, involving differentiation of pluripotent stem cells into T cells in the presence of mesenchymal stem cells or their products, using specific cytokines, antibodies, and culture conditions to induce regenerative activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If mesenchymal cells are administered via intravenous injection, then they can reach target tissues, but they are blocked by pulmonary circulation due to their large size
Solution Approach 1:
The patent changes the key parameter of cell size by differentiating pluripotent stem cells into T cells, which are significantly smaller than mesenchymal cells. This size reduction allows the cells to bypass pulmonary blockade and successfully reach target tissues through intravenous administration.
2Productivity
If donor cells are used for therapy, then treatment can be provided, but donor-to-donor variability causes inconsistent clinical results
Solution Approach 1:
The patent creates a universal cell source by differentiating pluripotent stem cells into T cells. These T cells can be used for multiple therapeutic purposes and can be standardized to reduce donor-to-donor variability, thereby improving consistency of clinical results while maintaining therapeutic efficacy.
Solution Approach 2:
The patent performs preliminary differentiation of pluripotent stem cells into T cells with desired characteristics before administration. This preliminary action allows for standardization and quality control, ensuring consistent therapeutic results by pre-establishing the functional properties of the cells.
3Reliability
If pluripotent stem cells are differentiated into T cells, then regenerative activity is achieved, but complex differentiation protocols are required
Solution Approach 1:
The patent uses mesenchymal stem cells or their products as intermediaries during the differentiation process. These intermediary elements facilitate the differentiation of pluripotent stem cells into T cells with regenerative activity, making the complex process more controllable and reliable.
Data Source
AI summary
Disclosed are novel cellular compositions of matter and treatment means for generation of universal donor regenerative T cells by exposure to mesenchymal stem cells or supernatant derived thereof. In one embodiment, regenerative T cells are created by differentiation of pluripotent stem cells in the presence of supernatant generated from activated mesenchymal stem cell population. The invention provides for creation of T cells which are capable of endowing regenerative activity, and/or anti-inflammatory, and/or angiogenic activity.