Mesenchymal Cell Population for Rapid Cell Sheet Production
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Solution Overview
Problem
Existing cell transplantation therapies face challenges in integrating cells into tissues, and there is a need for a cost-effective method to produce cell sheets with specific cell surface antigen molecules for therapeutic applications.
Innovation Solution
A cell population is developed containing 80% or more mesenchymal cells expressing CD13, CD59, CD49e, CD151, and/or CD280, derived from intraoral tissues, which can be cultured to form a cell sheet or three-dimensional culture, and used in pharmaceutical compositions for treating conditions like refractory skin ulcers and ischemic tissues.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If fibroblasts are used as cell sheet material with strong proliferation ability, then cell production efficiency is improved, but cell sheet integration into tissue is insufficient
Solution Approach 1:
The patent applies local quality by selecting fibroblasts with specific surface antigen expressions (CD106, CD274, HLA-DP/DQ/DR) rather than uniform fibroblast populations. This creates localized functional differences within the cell population, where cells expressing specific antigens contribute to different functions: CD106 for angiogenesis and tissue integration, CD274 for immune modulation, and HLA molecules for immune compatibility. This resolves the contradiction by having different cell subpopulations specialize in either proliferation or integration/immune functions.
Solution Approach 2:
The patent creates a composite cell population combining fibroblasts with specific surface antigen profiles. This composite approach integrates multiple functional characteristics into a single cell population: the proliferative capacity of fibroblasts, the angiogenic properties of CD106-expressing cells, the immune modulatory effects of CD274-expressing cells, and the immune compatibility provided by HLA molecules. This composite cell population simultaneously achieves high productivity and reliable tissue integration.
2Reliability
If cell culture time is extended to improve cell sheet quality, then cell integration ability is improved, but production cost increases
Solution Approach 1:
The patent applies parameter changes by optimizing culture conditions specifically for fibroblasts with selected surface antigen expressions. By adjusting parameters such as culture medium composition, oxygen tension, and temperature to match the specific antigen profile requirements, the cells achieve optimal proliferation and differentiation rates. This allows high-quality cell sheets with proper integration ability to be produced in reduced time compared to conventional culture methods, resolving the contradiction between quality and production time.
3Reliability
If specific cell surface antigen molecules are expressed to improve tissue integration, then cell function is improved, but cell population complexity increases
Solution Approach 1:
The patent uses local quality by defining specific surface antigen expression patterns (CD106, CD274, HLA-DP/DQ/DR) as quality markers for fibroblast functionality. Rather than creating a complex mixture of many different cell types, the patent focuses on selecting fibroblasts that express these particular antigens at appropriate levels. This creates a functionally heterogeneous but structurally simple population where antigen expression levels and patterns indicate specific functional capabilities, resolving the contradiction between improved tissue integration and population complexity.
Data Source
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AI summary
An object of the present disclosure is to provide a cell population isolated from a living organism, which contains mesenchymal cells capable of being utilized in cell sheet production and has a specific cell surface antigen molecule. A cell population isolated from a living organism and containing 80% or more of mesenchymal cells expressing at least one cell surface antigen molecule selected from the group consisting of CD13, CD59, CD49e, CD151, and CD280 is used. Preferably, the mesenchymal cells are cells collected from an intraoral tissue or a culture thereof, and the mesenchymal cells express at least three or more cell surface antigen molecules selected from the group consisting of CD13, CD59, CD49e, CD151, and CD280.