Culture Medium for Ex Vivo Hematopoietic Cell Expansion

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Solution Overview

Problem

Current methods for the expansion and long-term maintenance of human erythroblast, megakaryocyte-erythroid progenitor, and common myeloid progenitor cells ex vivo are limited in capacity and effectiveness, hindering their clinical applications.

Innovation Solution

A culture medium comprising a tankyrase inhibitor, a B-Raf kinase inhibitor, and a GSK-3 inhibitor, along with a growth factor like stem cell factor, supports the long-term expansion and maintenance of these cells, allowing for significant expansion and differentiation capabilities.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional culture methods with multiple growth factors are used, then cell expansion is attempted, but the expansion capacity is limited and long-term maintenance is not achieved

Engineering Contradiction:
Improvecell expansion capacityVSAvoidlong-term maintenance duration
Core Design Contradiction:
ProductivityVSDuration of action of stationary object

Solution Approach 1:

The patent changes the chemical parameters of the culture medium by incorporating specific inhibitors (tankyrase inhibitor, B-Raf kinase inhibitor, GSK-3 inhibitor) at optimized concentrations. This parameter modification enables both high expansion capacity (50-10,000 folds) and long-term maintenance (over 2 weeks), resolving the contradiction between expansion productivity and maintenance duration that plagues conventional methods.

Inventive Principle:
Principle #35Parameter changes

2Productivity

If multiple growth factors are combined for cell expansion, then some expansion is achieved, but the method complexity increases and effectiveness remains limited

Engineering Contradiction:
Improvecell expansion efficiencyVSAvoidculture medium composition complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent extracts and isolates the key functional components needed for cell expansion by using specific inhibitors (tankyrase inhibitor, B-Raf kinase inhibitor, GSK-3 inhibitor) instead of complex combinations of multiple growth factors. This extraction approach simplifies the culture medium composition while maintaining or improving expansion efficiency, directly addressing the contradiction between productivity and complexity.

Inventive Principle:
Principle #2Taking out (Extraction)

3Quantity of substance

If cells are expanded ex vivo, then cell quantity increases, but morphological integrity and differentiation capacity may be compromised

Engineering Contradiction:
Improvecell quantityVSAvoidmorphological integrity and differentiation capacity
Core Design Contradiction:
Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent applies prior cushioning by pre-treating cells with a carefully formulated culture medium containing specific inhibitors before expansion. This protective measure ensures that even as cell quantity increases dramatically (50-10,000 folds), the cells maintain their morphological integrity and differentiation capacity, preventing the degradation that typically occurs during ex vivo expansion.

Inventive Principle:
Principle #11Beforehand cushioning (Prior cushioning)

Data Source

PatentUS11970713B2Method for long-term ex vivo maintenance or expansion of human erythroblast, human megakaryocyte-erythroid progenitor, or human common myeloid progenitor cell and application thereof
Publication Date: 2024.04.30 OCGENE THERAPEUTICS CORP
  • US11970713B2 patent drawing
  • US11970713B2 patent drawing
  • US11970713B2 patent drawing

AI summary

The invention relates to a method for long-term ex vivo maintenance or expansion of one or more of a human erythroblast, a human megakaryocyte-erythroid progenitor, or a human common myeloid progenitor, comprising the step of: culturing cells comprising one or more of those cells in a culture medium comprising one or more selected from a tankyrase inhibitor, a growth factor, a B-Raf kinase inhibitor and a GSK-3 inhibitor.