Mesenchymal Stem Cell Reprogramming via Synthetic RNA

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Solution Overview

Problem

Current methods for obtaining mesenchymal stem cells (MSCs) face challenges such as declining cell numbers and differentiation potential with increasing donor age, inconsistent quality of bone marrow-derived MSCs, and the invasive nature of bone marrow aspiration procedures, necessitating the development of alternative, consistent, and reliable sources for therapeutic use.

Innovation Solution

The method involves reprogramming induced pluripotent stem cells (iPSCs) into MSCs using synthetic RNA molecules encoding reprogramming factors, followed by assaying for a specific protein secretion signature that includes increased secretion of certain proteins and decreased secretion of others relative to bone marrow-derived MSCs, resulting in a consistent and effective therapeutic cell population.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If bone marrow aspiration is used to obtain MSCs, then therapeutic cell material can be obtained, but the procedure is invasive and quality is inconsistent

Engineering Contradiction:

Improvequality consistency of MSCsVSAvoidinvasiveness of bone marrow aspiration

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses induced pluripotent stem cells (iPSCs) as a copy or alternative source to replace bone marrow-derived MSCs. iPSCs can be generated from non-invasive sources like skin biopsies or blood, and then differentiated into MSCs that function similarly to bone marrow-derived MSCs, thereby avoiding the invasive aspiration procedure while maintaining therapeutic efficacy

Inventive Principle:

Principle #26Copying

Solution Approach 2:

The patent employs mRNA-based reprogramming factors (such as OCT4, SOX2, KLF4, and c-MYC) to fundamentally change the cellular parameters and state of the source cells. By introducing these reprogramming factors, the patent transforms the differentiation potential and properties of the cells to generate consistent, high-quality MSCs regardless of donor age or bone marrow quality

Inventive Principle:

Principle #35Parameter changes

2Reliability

If bone marrow-derived MSCs are used, then therapeutic effects can be achieved, but cell numbers and differentiation potential decline with increasing donor age

Engineering Contradiction:

Improvetherapeutic effectivenessVSAvoidnumber and differentiation potential of MSCs

Core Design Contradiction:

ReliabilityVSQuantity of substance

Solution Approach 1:

The patent creates a bypass to the age-related degradation of bone marrow MSCs by using iPSCs as a renewable source. Since iPSCs can be derived from various sources and expanded indefinitely in culture, they provide a consistent supply of young, undifferentiated cells that can be differentiated into MSCs with full differentiation potential, regardless of the donor's age

Inventive Principle:

Principle #26Copying

Solution Approach 2:

The patent performs preliminary reprogramming of somatic cells into iPSCs before differentiation into MSCs. This preliminary action resets the cellular clock and restores full differentiation potential, ensuring that the resulting MSCs have the same regenerative capacity as those from young donors, thereby solving the age-related decline problem

Inventive Principle:

Principle #10Preliminary action

3Reliability

If iPSCs are reprogrammed into MSCs using mRNA-based methods, then consistent and reliable MSC populations are obtained, but the process complexity increases

Engineering Contradiction:

Improvetherapeutic reliability and consistencyVSAvoidcomplexity of reprogramming process

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent replaces traditional mechanical or chemical reprogramming methods with mRNA-based delivery. Instead of using viral vectors or complex transfection protocols, the patent uses in vitro transcribed mRNA that can be delivered to cells and translated into reprogramming factors, simplifying the process while improving consistency and reducing contamination risks

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent uses mRNA as an intermediary carrier to deliver reprogramming information into cells. This intermediary approach allows for precise control over the reprogramming process, enables batch production of standardized reprogramming factors, and facilitates quality control through mRNA sequencing and validation before cell treatment

Inventive Principle:

Principle #24Intermediary (Mediator)

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 yields MSCs with enhanced therapeutic reliability and consistency, offering improved therapeutic effects and reducing inflammation and immunogenicity, while allowing for allogeneic use and in vitro expansion without substantial loss of immunosuppressive properties.

Implementation Method 1

reprogramming an induced pluripotent stem cell (iPSC) into a mesenchymal stem cell (MSC), the reprogramming comprising contacting the iPSC with one or more synthetic RNA molecules encoding a reprogramming factor

Methodology Applied

Scientific EffectmRNA-based reprogramming:

Data Source

PatentUS20230193207A1Mesenchymal stem cell therapies

Publication Date: 2023.06.22 FACTOR BIOSCIENCE INC

AI summary

Cell-based therapies based on mesenchymal stem cells (MSCs) are described.