Muse Cell Guidance via S1P Receptor Activation
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Solution Overview
Problem
Current methods for guiding pluripotent stem cells, specifically Muse cells, to damaged tissue sites are inefficient due to unknown chemotactic mechanisms and high tumorigenic potential of iPS cells, limiting their therapeutic application in tissue regeneration.
Innovation Solution
Identification and utilization of sphingosine-1-phosphate (S1P) as a chemotactic factor that activates S1P receptor 2 in Muse cells, enhancing their migratory activity and accumulation at damaged sites through a pharmaceutical composition, which includes S1P agonists and inhibitors, ensuring safe and effective tissue regeneration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If iPS cells are used for tissue regeneration, then pluripotent stem cell availability is improved, but tumorigenic potential increases
Solution Approach 1:
The invention extracts and isolates Muse cells from mesenchymal stem cell fractions through specific surface marker identification (SSEA-3 positive, CD105 positive). This extraction process separates the desired pluripotent stem cells with low tumorigenicity from other cell types, achieving both pluripotent stem cell availability and reduced tumorigenic risk
Solution Approach 2:
The invention uses naturally occurring Muse cells that can be obtained without complex induction procedures. These cells are readily available in mesenchymal tissue and can be harvested and applied directly, avoiding the need for expensive and complex iPS cell reprogramming while providing sufficient cell quantity for therapy
2Reliability
If Muse cells are used for tissue regeneration, then tissue repair capability is improved, but chemotactic guidance mechanism is unknown
Solution Approach 1:
The invention identifies S1P as the chemotactic factor that guides Muse cells to damaged tissue. By understanding this feedback mechanism where damaged tissue releases S1P that attracts Muse cells via S1P receptor 2, the natural guidance system is harnessed to improve tissue repair reliability
Solution Approach 2:
The invention introduces S1P agonists as intermediary substances that mediate the chemotactic guidance of Muse cells to damaged sites. These agonists act as substitutes for the natural S1P signal, ensuring Muse cells can be effectively guided even when endogenous S1P levels are insufficient
3Quantity of substance
If complex induction procedures are used to obtain iPS cells, then pluripotent stem cell production is achieved, but procedure complexity increases
Solution Approach 1:
The invention utilizes Muse cells that naturally exist in mesenchymal tissue and can be obtained through simple fractionation and surface marker selection. The cells serve themselves by naturally migrating to damaged sites when S1P signaling is activated, eliminating the need for complex reprogramming procedures and providing a self-sufficient therapeutic approach
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 pharmaceutical composition effectively guides Muse cells to damaged sites, enhancing their chemotactic activity and facilitating tissue regeneration by activating S1P receptor 2, thereby overcoming previous limitations in therapeutic application and tumorigenic risks.
Implementation Method 1
Identification and utilization of sphingosine-1-phosphate (S1P) as a chemotactic factor that activates S1P receptor 2 in Muse cells, enhancing their migratory activity and accumulation at damaged sites
Data Source
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AI summary
The purpose of the present invention is to identify a migratory factor that guides pluripotent stem cells (Muse cells) useful in new medical applications to damage, and to provide a pharmaceutical composition that includes the migratory factor for promoting tissue regeneration in regenerative medicine that makes use of Muse cells. In the present invention, a receptor that is specifically expressed in Muse cells rather than non-Muse cells was identified, and it was confirmed that a ligand for this receptor can function as a migratory factor. In the present invention, sphingosine-1-phosphate (S1P) was identified as a migratory factor, and thus, the present invention pertains to a pharmaceutical composition for guiding pluripotent stem cells to damage, the composition including SIP as an active ingredient.