Effects of Heparin and Its 6-O-and 2-O-Desulfated Derivatives with Low Anticoagulant Activity on Proliferation of Human Neural Stem/Progenitor Cells(CELL AND TISSUE ENGINEERING, <Special Issue>Advances in Biomedical Science and Engineering)

概要

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Heparin binds various growth factors and activates them to interact with high-affinity cell surface receptors; a specific array of sulfate groups in the heparin backbone structure is very important for this interaction. In the present study, we evaluated the effects of two novel heparin derivatives, 6-O-desulfated heparin (6-DSH) and 2-O-desulfated heparin (2-DSH), on blood coagulation and the proliferation of human neural stem/progenitor cells (NSPCs). 6-DSH showed lower anticoagulant activity than intact heparin or 2-DSH, as measured by the activated partial thromboplastin time and thrombin time. In the presence of FGF-2, 6-DSH and 2-DSH promoted approximately the same rate of proliferation of human NSPCs, without noticeably changing the expression of nestin. The mitotic effects of 6-DSH and 2-DSH on human NSPCs were different from their effects on mouse hematopoietic stem cells and fibroblasts. These findings indicate that 6-DSH and 2-DSH have the same ability to promote the growth of human NSPCs as intact heparin. Our results suggest that these two novel heparin derivates, especially 6-DSH, could be used in clinical applications for ex vivo human NSPC culture, as a lower-risk growth co-adjuvant than intact heparin.
社団法人日本生物工学会の論文
2005-07-25