Fetal Appendage Cell Population Selection for Ectopic Tissue Risk
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Solution Overview
Problem
Current methods for producing adherent cells from fetal appendages result in heterogeneous cell populations with varying differentiation and proliferative capacities, leading to risks of ectopic tissue formation and reduced safety when used as cell preparations for immune-related and inflammatory diseases.
Innovation Solution
A method is developed to produce a cell population with a high proportion of CD73 and CD90-positive cells and specific gene expression levels (LFA-3, CCND2, and HAPLN1 relative to SDHA), ensuring low differentiation capacity and safety by using these characteristics as indices.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If adherent cells derived from fetal appendage are used as a cell preparation, then the ability to secrete cytokines involved in immunosuppression is improved, but the risk of ectopic tissue formation increases due to high differentiation capacity
Solution Approach 1:
The patent extracts and isolates specific cell populations from the heterogeneous adherent cell population by using surface antigen markers (CD73, CD90, STRO-1) as identification criteria. This extraction process separates cells with desired immunosuppressive functions from cells with high differentiation capacity that could cause ectopic tissue formation, thereby resolving the contradiction between therapeutic efficacy and safety.
Solution Approach 2:
The patent applies local quality by defining specific phenotypic characteristics (CD73+, CD90+, STRO-1-) for the cell population intended for therapy. By specifying these local quality markers, the patent ensures that only cells with the desired functional properties (immunosuppression) and reduced differentiation capacity are selected, thus maintaining therapeutic efficacy while minimizing harmful effects.
2Productivity
If a heterogeneous cell population is used, then the cell preparation has high proliferative capacity, but the quality stability and safety are reduced
Solution Approach 1:
The patent changes the selection parameters for cell population definition by using specific surface antigen expression patterns (CD73+, CD90+, STRO-1-) as inclusion/exclusion criteria. This parameter change transforms the heterogeneous population into a homogeneous, well-defined cell population with stable quality attributes while preserving the desired proliferative and immunosuppressive functions.
3Adaptability or versatility
If cells with high differentiation capacity are administered, then the cell preparation has high therapeutic potential, but the safety is compromised due to ectopic tissue formation
Solution Approach 1:
The patent extracts cells with specific phenotypic characteristics (CD73+, CD90+, STRO-1-) from the total cell population. This extraction isolates cells that maintain therapeutic potential through immunosuppressive cytokine secretion while removing or reducing cells with high differentiation capacity that could form ectopic tissues, thereby resolving the safety concern.
Solution Approach 2:
The patent defines local quality markers (surface antigen expression profiles) that identify cells with appropriate functional characteristics for therapy. By selecting cells that are CD73+, CD90+, and STRO-1-, the patent ensures a balance between maintaining therapeutic adaptability (immunosuppression) and ensuring safety (reduced differentiation capacity).
Data Source
AI summary
An object of the present invention is to provide a cell population comprising adherent cells having low differentiation capacity derived from a fetal appendage, methods for producing or using the same, and a pharmaceutical composition comprising the cell population, in particular wherein the proportion of CD73- and CD90-positive adherent cells derived from a fetal appendage is 90% or more; and the cell population satisfies a relative expression level of LFA-3 gene to the expression level of SDHA gene of 1.0 or more, in particular wherein the relative expression level of HAPLN1 gene to the expression level of SDHA gene is 4.0 or more and/or the relative expression level of CCND2 gene to the expression level of SDHA gene is 1.5 or less, in particular wherein the proportion of the STRO-1-negative adherent cells derived from a fetal appendage is 95% or more.