Induced Smooth Muscle Cells via Skeletal Cell Transdifferentiation

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Solution Overview

Problem

Current methods for obtaining smooth muscle cells are limited by the availability of primary smooth muscle cells, which are heterogeneous and have limited proliferative capacity, and alternative cell therapies like iPSCs pose safety concerns, while skeletal muscle-derived cells (SMDCs) lack clear differentiation and regenerative pathways for smooth muscle tissue.

Innovation Solution

A method involving the transdifferentiation of skeletal muscle-derived cells (SMDCs) using TGF-beta and heparin in a specific medium to obtain induced smooth muscle cells (iSMCs) that express markers like aSMA, CD49a, and CD146, ensuring safety and effectiveness for smooth muscle regeneration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If primary smooth muscle cells are used for smooth muscle regeneration, then smooth muscle tissue can be regenerated, but the cells are heterogeneous and have limited proliferative capacity

Engineering Contradiction:

Improvesmooth muscle regeneration capabilityVSAvoidproliferative capacity

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent changes the biological parameters of the cells by using induced pluripotent stem cells (iPSCs) that can be differentiated into smooth muscle cells. These iPSC-derived smooth muscle cells maintain the regenerative capability while possessing high proliferative capacity, thus resolving the contradiction between reliability and productivity.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent performs preliminary differentiation of iPSCs into smooth muscle progenitor cells before transplantation. This preliminary action ensures that the cells are pre-programmed to become smooth muscle cells, maintaining tissue-specific regenerative capability while allowing extensive in vitro proliferation to expand cell numbers.

Inventive Principle:

Principle #10Preliminary action

2Productivity

If induced pluripotent stem cells (iPSCs) are used for smooth muscle differentiation, then smooth muscle cells can be obtained with high proliferative capacity, but safety concerns arise due to genetic instability and teratoma formation

Engineering Contradiction:

Improveproliferative capacityVSAvoidgenetic instability and teratoma formation

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent uses partial differentiation of iPSCs into smooth muscle progenitor cells rather than complete differentiation. This partial action approach allows the cells to acquire smooth muscle characteristics and proliferative capacity while reducing the risk of teratoma formation compared to using fully undifferentiated iPSCs.

Inventive Principle:

Principle #16Partial or excessive action

Solution Approach 2:

The patent generates smooth muscle cells by differentiating iPSCs, creating a copy of the desired cell type with controlled properties. This allows selection and expansion of cells with appropriate characteristics while avoiding the genetic instability issues of reprogrammed cells through careful differentiation protocols.

Inventive Principle:

Principle #26Copying

3Ease of manufacture

If skeletal muscle-derived cells (SMDCs) are used for treatment, then cells are readily accessible and highly proliferative, but the differentiation pathway to smooth muscle tissue is unclear

Engineering Contradiction:

Improvecell accessibilityVSAvoiddifferentiation pathway information

Core Design Contradiction:

Ease of manufactureVSLoss of information

Solution Approach 1:

The patent uses TGF-beta signaling as an intermediary mechanism to guide the transdifferentiation of SMDCs into smooth muscle cells. This intermediary pathway provides the missing differentiation information, enabling SMDCs to convert into smooth muscle cells through a defined molecular pathway rather than direct transdifferentiation.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the phenotypic parameters of SMDCs through transdifferentiation induced by TGF-beta signaling. This parameter change transforms the cells from a skeletal muscle phenotype to a smooth muscle phenotype, providing the necessary differentiation pathway information while maintaining the ease of cell acquisition.

Inventive Principle:

Principle #35Parameter changes

4Reliability

If smooth muscle tissue is used as a source for cell therapy, then functional smooth muscle cells can be obtained, but the tissue is hardly accessible in living humans for autologous treatment

Engineering Contradiction:

Improvefunctional smooth muscle cell qualityVSAvoidtissue accessibility

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent inverts the traditional approach by not using smooth muscle tissue directly as the source, but rather using easily accessible cells (SMDCs or iPSCs) that can be differentiated into smooth muscle cells. This inversion resolves the accessibility problem while maintaining the functional quality of smooth muscle cells through controlled differentiation.

Inventive Principle:

Principle #13The other way round (Inversion)

Data Source

PatentUS20250207097A1Methods for obtaining induced smooth muscle cells

Publication Date: 2025.06.26 INNOVACELL GMBH

AI summary

The present invention relates to methods for obtaining induced smooth muscle cells (iSMCs), iSMCs, iSMCs for use in a method of treating a disease or disorder or for use in tissue engineering, and the use of skeletal muscle derived cells for obtaining iSMCs.