Hematopoietic Stem Cell Marker Set for Enrichment

Solution Overview

Problem

Current methods for isolating long-term hematopoietic stem cells are inefficient and require extensive trial and error, involving costly and time-consuming processes to identify specific surface molecules, making it difficult to enrich these cells effectively for regenerative medicine applications.

Innovation Solution

A marker set comprising CD10, CD111, CD112, CD131, CD143, CD244, CD275, CD328, CD62L, GPR56, CD133, CD36, CD370, CD84, CD326, CD114, CD116, CD135, CD172a/b, CD200, CD226, CD245, CD31, CD317, CD40, CD41, CD61, CD93, Notch1, CD352, Siglec-10, CD45RO, CD11c, CD52, CD318, CD49f, c-Kit, and CD48 is used to enrich or isolate hematopoietic stem cells, allowing for more accurate and efficient identification and isolation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional methods using trial and error to identify combinations of monoclonal antibodies are used, then hematopoietic stem cells can be identified, but the process requires huge amounts of time and cost

Engineering Contradiction:

Improveidentification accuracy of long-term HSCsVSAvoiddevelopment time

Core Design Contradiction:

Measurement precisionVSLoss of time

Solution Approach 1:

The patent applies preliminary action by pre-identifying and establishing a specific combination of surface molecules (CD34-, CD38-, CD45RA-, Thyl+) that characterizes long-term HSCs before actual isolation procedures. This pre-established marker profile eliminates the need for time-consuming trial and error in each new isolation attempt, allowing researchers to directly apply the known marker combination to enrich long-term HSCs from cord blood samples.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent uses copying by replicating the successful mouse HSC identification approach (using surface molecule combinations) and adapting it to human cord blood samples. By copying the methodological framework from mouse models and applying it to human samples with specific modifications, the patent accelerates the identification process without requiring entirely new development approaches.

Inventive Principle:

Principle #26Copying

2Measurement precision

If conventional methods using trial and error to identify combinations of monoclonal antibodies are used, then hematopoietic stem cells can be identified, but the process requires huge amounts of cost

Engineering Contradiction:

Improveidentification accuracy of long-term HSCsVSAvoiddevelopment cost

Core Design Contradiction:

Measurement precisionVSLoss of substance

Solution Approach 1:

The patent applies preliminary action by pre-identifying and establishing a specific combination of surface molecules (CD34-, CD38-, CD45RA-, Thyl+) that characterizes long-term HSCs before actual isolation procedures. This pre-established marker profile eliminates the need for time-consuming trial and error in each new isolation attempt, allowing researchers to directly apply the known marker combination to enrich long-term HSCs from cord blood samples.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent uses copying by replicating the successful mouse HSC identification approach (using surface molecule combinations) and adapting it to human cord blood samples. By copying the methodological framework from mouse models and applying it to human samples with specific modifications, the patent accelerates the identification process without requiring entirely new development approaches.

Inventive Principle:

Principle #26Copying

3Productivity

If existing marker combinations (CD34+, CD38-, CD45RA-) are used to enrich hematopoietic stem cells, then cell enrichment can be achieved, but the fraction still contains various cells with different abilities to maintain stem cell characteristics

Engineering Contradiction:

Improveenrichment efficiencyVSAvoidpurity of long-term HSCs

Core Design Contradiction:

ProductivityVSManufacturing precision

Solution Approach 1:

The patent applies segmentation by dividing the enrichment process into multiple sequential steps using different marker combinations. First, cells are selected for CD34 positivity, then further refined by selecting for CD38 negativity, CD45RA negativity, and Thyl positivity. This multi-stage segmentation approach progressively purifies the long-term HSC population by eliminating different cell types at each stage, achieving both high enrichment efficiency and high purity.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent applies local quality by using different marker specificity thresholds at different stages of enrichment. Each marker (CD34, CD38, CD45RA, Thyl) is used with specific positivity or negativity criteria tailored to the enrichment stage, allowing precise control over which cell populations are retained or excluded at each step of the process.

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS20230279354A1Human long-term hematopoietic stem cell marker

Publication Date: 2023.09.07 NEXTGEM INC

AI summary

The present disclosure relates to a marker for enriching or isolating hematopoietic stem cells and a method for using the same, cells or a cell population isolated or enriched by the marker, a method for using the cells or cell population, a drug containing the cells or cell population, and a classifier obtained using the cells or cell population.