Selective Surface for Apoptosis-Resistant Cell Enrichment
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Solution Overview
Problem
Current medical technologies face challenges in selectively isolating apoptosis-signaling resistant stem and progenitor cells, which are crucial for transplantation therapies, as existing methods fail to effectively differentiate and enrich these cells while avoiding graft versus host disease (GvHD) and maintaining graft versus tumor (GvT) activity.
Innovation Solution
A selective surface comprising a biocompatible polymer with maleic anhydride molecules and an immobilized apoptosis-inducing ligand, such as FasL, is used to selectively bind and enrich apoptosis-signaling resistant cells, including stem and progenitor cells, by incubating cell populations with the surface to eliminate sensitive cells, thereby reducing the risk of GvHD while retaining GvT activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If existing methods are used to isolate stem and progenitor cells, then cell isolation is performed, but apoptosis-signaling resistant cells cannot be effectively enriched and GvHD risk remains
Solution Approach 1:
The patent converts the harmful effect of apoptosis-inducing ligands (which normally cause cell death) into a beneficial selection mechanism. By immobilizing FasL on the container surface, apoptosis-sensitive cells are eliminated while apoptosis-resistant stem and progenitor cells survive and are enriched, thus transforming a harmful apoptotic signal into a useful cell selection tool
Solution Approach 2:
The patent applies local quality by creating a selective surface with specific apopticity only where needed - the inner surface of the container is modified with apoptosis-inducing ligands, while the bulk medium and other surfaces remain non-selective. This localized application allows precise control over which cells are selected without affecting the entire system uniformly
2Reliability
If apoptosis-inducing ligands are used to select cells, then apoptosis-resistant cells are enriched, but maintaining biological activity of the ligand on the surface is challenging
Solution Approach 1:
The patent uses maleic anhydride molecules as an intermediary between the container surface and the apoptosis-inducing ligand. The maleic anhydride forms a reactive layer on the surface that enables covalent bonding of FasL, serving as a mediator that facilitates stable ligand attachment while preserving ligand biological activity
Solution Approach 2:
The patent creates a composite surface structure combining the container material (polystyrene or fluorocarbon polymer) with maleic anhydride functional groups and immobilized apoptosis-inducing ligands. This composite structure integrates the mechanical properties of the container with the selective biological function of the ligand layer
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 method effectively enriches apoptosis-signaling resistant cells, improving the clinical outcome of hematopoietic stem and progenitor cell transplantation by reducing malignant cell contamination and minimizing GvHD while maintaining immune function, as demonstrated by the selective elimination of apoptosis-sensitive cells and preservation of graft activity.
Implementation Method 1
a biocompatible polymer comprising maleic anhydride molecules; and an apoptosis inducing ligand bound to the maleic anhydride molecules
Data Source
Figure 1A~1B
Figure 2A~2B
Figure 2C
AI summary
The present invention discloses selective surfaces, wherein said selective surfaces comprise a biocompatible polymer comprising maleic anhydride molecules and an apoptosis inducing ligand bound to the maleic anhydride molecules. The invention also encompasses devices and kits comprising the selective surface and methods for its production. The selective surfaces may be used for functional selection of cell populations suitable for transplantation into human subjects.