CD31/CD200-Positive, CD45-Negative Cells for Vascular Regeneration

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Solution Overview

Problem

Existing technologies fail to identify and utilize vascular endothelial stem cells effectively for vascular regeneration and treatment of related conditions, as these cells were believed to be absent in the blood vascular system.

Innovation Solution

A cell population of mammalian cells identified by CD31-positive, CD45-negative, CD200-positive and CD31-positive, CD157-positive, CD200-positive markers, which includes vascular endothelial stem cells, capable of self-renewal and differentiation, and a medicament comprising these cells for vascular regeneration and disease treatment.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If vascular endothelial cells are considered slowly dividing mature cells generated during the fetal period, then the blood vessels can be maintained throughout life, but vascular regeneration and stem cell identification are impossible

Engineering Contradiction:
Improveblood vessel maintenanceVSAvoidvascular regeneration capability
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent segments the vascular endothelial cell population into two distinct subsets: SP cells (side population) with stem cell characteristics and MP cells (main population) with mature characteristics. This segmentation allows the SP cells to provide regeneration capability while the MP cells maintain the blood vessels, resolving the contradiction between maintenance and regeneration.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent extracts and identifies the stem cell subset (SP cells) from the bulk mature cell population (MP cells) using flow cytometry based on Hoechst 33342 efflux capability. This extraction enables the isolation and utilization of regenerative potential while maintaining the overall vascular structure.

Inventive Principle:
Principle #2Taking out (Extraction)

2Measurement precision

If tissue-resident stem cells are identified using Hoechst efflux capability, then stem cell population can be isolated, but the identification method is complex and requires specialized reagents

Engineering Contradiction:
Improvestem cell identification accuracyVSAvoidisolation method complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent utilizes the fluorescent properties of Hoechst 33342 dye, which binds to DNA and emits fluorescence, to detect and sort stem cells based on their efflux capability. The fluorescent signal provides a clear distinction between SP and MP cells, enabling precise identification through flow cytometry.

Inventive Principle:
Principle #32Color changes

3Productivity

If bone marrow-derived vascular endothelial progenitor cells are used for revascularization, then vascular regeneration can occur, but the cells cannot continuously serve as vascular endothelial cells

Engineering Contradiction:
Improvevascular regenerationVSAvoidcontinuous service capability
Core Design Contradiction:
ProductivityVSDuration of action of stationary object

Solution Approach 1:

The patent identifies self-renewing stem cells within the vascular system itself (SP cells in preexisting blood vessels) that can continuously generate vascular endothelial cells without requiring external bone marrow input. This self-service capability resolves the limitation of transient progenitor cells.

Inventive Principle:
Principle #25Self-service

Data Source

PatentUS20250257326A1Cell populations of CD31-positive, CD45-negative, CD200-positive mammalian cells and use thereof
Publication Date: 2025.08.14 OSAKA UNIVERSITY
  • US20250257326A1 patent drawing
  • US20250257326A1 patent drawing
  • US20250257326A1 patent drawing

AI summary

Provided are a cell population substantially consisting of mammalian cells that are positive for cell surface markers CD31 and CD200 and negative for CD45; a cell population substantially consisting of mammalian cells that are positive for cell surface markers CD31, CD157 and CD200 and negative for CD45; a mammalian vascular endothelial stem cell that is positive for the cell surface marker CD31, positive for at least one of CD157 and CD200, and negative for CD45; and a medicament for vascular regeneration, comprising any of the cell populations or the vascular endothelial stem cells as an active ingredient.