Regio-modified Heparin for Umbilical Cord Blood Stem Cell Expansion
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Solution Overview
Problem
Current methods for ex vivo expansion of human postembryonic stem and progenitor cells from umbilical cord blood result in limited cell expansion and inability to differentiate into immunocompetent lymphatic cells, restricting their therapeutic application due to small cell numbers and uncontrolled differentiation.
Innovation Solution
The use of a regio-modified glycan and/or glycosaminoglycan in a stroma-free medium, where the C2 atom is acylated or acetylated and the C6 atom is O-sulfated, allows for the expansion of stem and progenitor cells that can differentiate into myeloid and lymphatic cells, maintaining stem cell properties and enabling their use as immunotherapeutic agents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If stem cells are cultivated in stroma-free medium with conventional additives, then cell expansion is limited, but the method avoids unwanted differentiation
Solution Approach 1:
The patent applies parameter changes by modifying the chemical structure of heparin to create regio-modified glycosaminoglycans with specific sulfation patterns (6-O-sulfated, 2-O-desulfated). This structural modification changes the biological activity of the glycosaminoglycan, enabling it to support both high-level cell expansion and maintain differentiation potential simultaneously, resolving the contradiction between quantity and reliability
2Quantity of substance
If stem cells are expanded using prior art methods, then cell numbers increase slightly, but the cells lose capability to differentiate into lymphatic cells
Solution Approach 1:
The patent changes the chemical parameters of the culture medium by introducing regio-modified glycosaminoglycans with specific sulfation patterns. This parameter change enables the medium to support expansion of cell numbers while preserving and even enhancing the differentiation capability into lymphatic cells, thereby resolving the contradiction between quantity and adaptability
3Quantity of substance
If conventional heparin is used in culture medium, then some cell expansion is achieved, but expansion of CD34+ cells is only 1.1-fold after seven days
Solution Approach 1:
The patent applies parameter changes by modifying the sulfation pattern of heparin to create 6-O-sulfated, 2-O-desulfated glycosaminoglycans. This chemical parameter change dramatically improves the productivity of cell expansion, achieving 180-fold expansion of TNC cells and 20-fold expansion of CD34+ cells, thereby resolving the contradiction between quantity and productivity
Data Source
AI summary
Method for obtaining and expanding postembryonic hematopoietic stem cells from umbilical cord blood while avoiding unwanted differentiation. Initial cells from umbilical cord blood are proliferated and multiplied ex vivo in a stroma-free medium and in the presence of a regio-modified glycan or glycosaminoglycan. The regio-modified glycan or glycosaminoglycan, e.g. a heparin derivative, is N-desulfated, and N-reacetylated or N-reacylated, in essence, on C2 atoms. The heparin derivative advantageously comprises less than 5 percent of C3-O-sulfate, at least 60 percent C2-O-sulfate, and it is preferably added in a quantity of 15 to 50 mg/L to the medium in order to stop an unwanted differentiation. The stem cells generated in this manner can differentiate, after expansion, into myeloma cells and lymphatic cells, and they can be used as an immunotherapeutic agent against many diseases.