Cell Purity via Contaminant Conversion and Segmented Enzyme Treatment

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Solution Overview

Problem

Current methods for cell transplantation face challenges in achieving high target cell purity, leading to suboptimal therapeutic effects due to the presence of contaminating cells, which complicates the purification process and reduces the efficacy of cell transplantation therapies.

Innovation Solution

A method involving the conversion of contaminating cells into distinct cell types, such as fat cells, megakaryocytes, or cardiac muscle cells, allowing for their efficient removal or separation from target cells like skeletal myoblasts, thereby enhancing target cell purity through techniques like filtration or centrifugation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If cells are cultured without purification of target cells, then the proliferation process is simple and fast, but the target cell purity decreases due to proliferation of other cells

Engineering Contradiction:
Improvecell proliferation speedVSAvoidtarget cell purity
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The patent applies preliminary action by performing enzyme treatment twice before cell proliferation: first treatment to initially separate cells from tissue, then a second treatment to further purify target cells. This preliminary purification sequence ensures high target cell purity is established before the proliferation phase begins, preventing contamination during subsequent culture expansion.

Inventive Principle:
Principle #10Preliminary action

2Productivity

If enzyme treatment is applied to separate target cells from tissue, then the separation efficiency improves, but the treatment time and process complexity increase

Engineering Contradiction:
Improvecell separation efficiencyVSAvoidenzyme treatment time
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

The patent implements periodic action by applying enzyme treatment in two distinct periods or stages: an initial enzyme treatment phase followed by a second enzyme treatment phase after intermediate processing. This periodic application of enzyme treatment optimizes separation efficiency at each stage while managing total treatment time through structured intervals rather than continuous prolonged exposure.

Inventive Principle:
Principle #19Periodic action

3Manufacturing precision

If multiple enzyme treatments are applied sequentially, then the target cell purity increases, but the process complexity and treatment time increase

Engineering Contradiction:
Improvetarget cell purityVSAvoidpurification process complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent applies segmentation by dividing the purification process into distinct sequential stages: first enzyme treatment, intermediate processing step, then second enzyme treatment. Each stage serves a specific purification function, with the first treatment performing initial separation and the second treatment providing refined purification. This segmented approach achieves high target cell purity while maintaining manageable process complexity through clear stage differentiation.

Inventive Principle:
Principle #1Segmentation

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

This approach significantly increases the purity of target cells, improving the therapeutic effect of cell transplantation by simplifying the purification process and enabling the treatment of larger cell quantities efficiently.

Implementation Method 1

separating cells from the tissue by a known method such as... enzyme treatment by immersion in a proteinase solution

Methodology Applied
Scientific EffectProteolysis: Hydrolysis

Implementation Method 2

the resulting enzyme treatment liquid is discarded, thereafter the skeletal muscle tissue is again subjected to an enzyme treatment

Methodology Applied
Scientific EffectCentrifugal separation: Centrifugal Separation

Data Source

PatentEP3064578B1Method of producing cell population with high target cell purity
Publication Date: 2021.01.13 TERUMO KK
  • EP3064578B1 patent drawingFigure 1

AI summary

The present invention relates to a method of producing a cell population with a high target cell purity, including: (1) a step of changing a character of contaminating cells in a cell population including target cells and the contaminating cells; and (2) a step of removing the contaminating cells and/or collecting the target cells, on the basis of the changed character. The invention also relates to: a cell population with a high target cell purity, produced by the method; a method of producing a sheet-shaped cell culture, including a step of culturing the cell population into a sheet shape; a sheet-shaped cell culture containing the cell population; a medical composition containing an effective component selected from the group including the cell population and the sheet-shaped cell culture; and a method of treating a disease in a subject, including a step of administering an effective amount of the cell population, the sheet-shaped cell culture or the medical composition, to the subject needing the same.