Pyrazole Compounds Expand Hematopoietic Stem Cells

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Solution Overview

Problem

Current methods for expanding hematopoietic stem cells and progenitor cells ex vivo are inefficient, costly, and pose risks of contamination or immune responses due to the use of foreign proteins and cells, with limited expansion efficacy and availability of donor sources.

Innovation Solution

The use of pyrazole compounds represented by a specific chemical formula to culture hematopoietic stem cells, which effectively expand CD34+ cells, CD34+CD38− cells, HPP-CFU colony forming cells, and SCID-repopulating cells, offering a safer and more cost-effective expansion method for hematopoietic stem cells and progenitor cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional methods using foreign proteins and cells are used to expand hematopoietic stem cells, then expansion efficacy is achieved, but contamination and immune response risks increase

Engineering Contradiction:
Improveexpansion efficacyVSAvoidcontamination and immune response risks
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent replaces expensive, complex foreign proteins and cells with a simple, small-molecule pyrazole compound that can be easily synthesized and discarded. This compound acts as a culture condition modulator rather than a biological agent, eliminating contamination and immune response risks while maintaining expansion efficacy.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The invention changes the fundamental parameter of the culture system from using complex biological agents (proteins and cells) to using a simple chemical compound. This parameter change transforms the expansion method from one requiring stringent contamination control to one that is inherently safer and more controllable.

Inventive Principle:
Principle #35Parameter changes

2Productivity

If conventional expansion methods are used, then some cell expansion is achieved, but treatment costs increase

Engineering Contradiction:
Improvecell expansionVSAvoidtreatment costs
Core Design Contradiction:
ProductivityVSEase of manufacture

Solution Approach 1:

The pyrazole compound is a small-molecule chemical that can be synthesized inexpensively through standard organic chemistry procedures, replacing costly recombinant proteins and cell-based products. This dramatically reduces treatment costs while maintaining expansion capability.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The invention extracts the essential function of expanding hematopoietic stem cells from complex biological systems and isolates it into a single, synthesizable chemical compound. This simplification removes the need for expensive production and purification processes associated with proteins and cells.

Inventive Principle:
Principle #2Taking out (Extraction)

3Quantity of substance

If bone marrow transplantation is performed, then hematopoietic stem cells are obtained, but donor availability is limited and hospitalization time increases

Engineering Contradiction:
Improvehematopoietic stem cellsVSAvoiddonor availability
Core Design Contradiction:
Quantity of substanceVSAdaptability or versatility

Solution Approach 1:

The patent enables preliminary expansion of hematopoietic stem cells ex vivo using the pyrazole compound before transplantation. This allows sufficient cell numbers to be obtained from limited donor sources, reducing the need for extensive donor searches and shortening hospitalization time.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The invention allows the hematopoietic stem cells to serve themselves by enabling their own expansion in culture through the pyrazole compound, eliminating the need for complex donor matching and extensive procurement procedures.

Inventive Principle:
Principle #25Self-service

Data Source

PatentUS9212348B2Method for producing hematopoietic stem cells using pyrazole compounds
Publication Date: 2015.12.15 NISSAN CHEM CORP
  • US9212348B2 patent drawing
  • US9212348B2 patent drawing
  • US9212348B2 patent drawing

AI summary

An expanding agent for hematopoietic stem cells and/or hematopoietic progenitor cells useful as a therapy for various hematopoietic diseases and useful for improvement in the efficiency of gene transfer into hematopoietic stem cells for gene therapy is provided.A method of producing hematopoietic stem cells and/or hematopoietic progenitor cells, which comprises expanding hematopoietic stem cells by culturing hematopoietic stem cells ex vivo in the presence of a compound represented by the formula following (I), a tautomer or pharmaceutically acceptable salt of the compound or a solvate thereof (wherein R1 to R8 are as defined in the description).