C1 Metabolite Cell Reprogramming for Progenitor State Induction
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Solution Overview
Problem
Current methods for investigating cellular differentiation focus on long-term time points, missing critical metabolic changes associated with the earliest transitional steps between cell phenotypes and fail to modulate cell fate effectively.
Innovation Solution
The use of specific metabolites, such as methionine, S-adenosyl methionine, threonine, glycine, putrescine, and cysteine, in cell culture media to reprogram cells from their steady state into a different cellular state, inducing de-differentiation or differentiation, thereby controlling cell fate.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If long term time points are used to assess cell state progression, then cell differentiation can be observed, but critical metabolic changes during earliest transitional steps are missed
Solution Approach 1:
The patent applies preliminary action by measuring metabolic parameters at multiple early time points (0, 1, 2, 3, 4, and 6 hours) during the initial differentiation transition, before the cells reach steady state. This early intervention in measurement captures the critical metabolic changes that occur during the earliest transitional steps, preventing loss of this temporal information.
Solution Approach 2:
The patent implements continuity of useful action by maintaining continuous measurement of metabolic parameters throughout the differentiation process at multiple time points. This continuous monitoring from 0 to 6 hours ensures that no critical metabolic changes are missed during the transition, providing uninterrupted insight into the differentiation dynamics.
2Stability of the object's composition
If steady state cell assessment is used, then cell phenotype is stable, but modulation of cell fate is not effective
Solution Approach 1:
The patent applies dynamics by transitioning from static steady-state assessment to dynamic multi-time-point measurement during the differentiation process. By capturing metabolic changes at multiple time points (0, 1, 2, 3, 4, 6 hours), the study reveals the dynamic metabolic reprogramming that occurs during cell fate transitions, enabling effective modulation of cell fate based on these dynamic changes.
3Quantity of substance
If metabolomic analyses are performed at steady state, then metabolite array is identified, but driver metabolites for cellular identity changes are not found
Solution Approach 1:
The patent applies preliminary action by performing metabolomic analyses at multiple early time points (0, 1, 2, 3, 4, 6 hours) during the initial differentiation transition, before cells reach steady state. This early measurement captures the driver metabolites that are actively changing during the transition process, preventing loss of information about which metabolites drive cellular identity changes.
Solution Approach 2:
The patent implements feedback by analyzing metabolic changes at multiple time points and using this information to identify driver metabolites that correlate with differentiation progression. The multi-time-point data allows for feedback-based identification of which metabolites are actually driving the cellular identity changes, rather than just observing steady-state metabolite arrays.
Data Source
AI summary
Compositions and methods modulating the steady state of cells are provided. The compositions include metabolites (C1 metabolites and C1 metabolite cocktails (C1-MIM) for use in inducing cells into a different state from their steady state, for example, into a less differentiated state, when compared to their original state before treatment. The C1 metabolites include methionine, SAM (S-adenosyl methionine), threonine, glycine, putrescine, and cysteine. The metabolites are used to supplement cell culture media, and accordingly, cells culture media supplemented with the disclosed metabolites (MIM supplemented media) are also provided.The method includes: contacting a cell with the C1 metabolites for a sufficient period of time to result in reprograming the cell into a different state from their steady, for example, into a less differentiated state having progenitor-like characteristics (MIM-Cells). Isolated MIM-cells and their progeny, can be used in a number of applications, including cell therapy and tissue engineering.