Stem Cell Expansion Compounds for Higher CD34+ Transplant Cell Yield
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Solution Overview
Problem
Current methods for expanding hematopoietic stem cells and progenitor cells are insufficient, leading to limited availability for transplantation, high transplant-related mortality, and immunodeficiency, particularly in cases where HLA-matched donors are unavailable or insufficient cell numbers are present.
Innovation Solution
The use of specific compounds, such as those described by formula I or their pharmaceutically acceptable salts, in combination with cell expanding agents, to enhance the ex vivo expansion of CD34+ cells, including CD34+CD45RA-, CD34+CD45RA+, and CD34+CD201+ cells, thereby increasing the number of available stem and progenitor cells for transplantation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If conventional methods are used for expanding hematopoietic stem cells, then the current limited expansion capability is maintained, but the availability of stem cells for transplantation remains insufficient
Solution Approach 1:
The patent applies parameter changes by modifying chemical parameters through the introduction of novel compounds with specific molecular structures (formula I) that have not been previously used in stem cell expansion. These compounds represent new chemical parameters that enable enhanced proliferation and expansion of hematopoietic stem cells, transforming the expansion capability from conventional limited growth to significant increase in cell numbers.
2Reliability
If HLA-matched donors are sought for transplantation, then transplant safety is improved, but the availability of suitable donors becomes limited
Solution Approach 1:
The patent applies preliminary action by expanding stem cells ex vivo before transplantation using the novel compounds. This preliminary expansion increases the cell dose available for transplantation, allowing patients to receive adequate stem cell doses even when HLA-matched donors are scarce or unavailable, thereby maintaining transplant safety while increasing donor availability.
3Reliability
If higher doses of stem cells are infused for transplantation, then the success and safety of transplant is improved, but the complexity of cell acquisition and expansion increases
Solution Approach 1:
The patent applies the intermediary principle by introducing novel chemical compounds (formula I) as mediators that facilitate stem cell expansion. These compounds act as intermediaries between the starting cell population and the desired high cell dose for transplantation, enabling controlled and efficient expansion without requiring complex mechanical or procedural systems.
4Quantity of substance
If stem cells are expanded ex vivo to increase availability, then the number of transplantable cells is improved, but the time required for expansion increases
Solution Approach 1:
The patent applies parameter changes by using novel compounds that alter the temporal parameters of stem cell expansion. These compounds enable rapid and efficient proliferation, significantly reducing the expansion time required to achieve transplantable cell doses compared to conventional methods, thus decreasing the loss of time while increasing the number of transplantable cells.
Data Source
Figure 1A~1B
Figure 1C~1D
Figure 2A
AI summary
The invention relates to compounds of formula I and pharmaceutical compositions containing them. Also, the invention relates to methods for expanding stem cells and/or progenitor cells and methods for treating a hematopoietic disorder/malignancy, and autoimmune disease and/or an inherited immunodeficient disease (I).