Effects of heparin and its 6-O-and 2-O-desulfated derivatives with low anticoagulant activity on proliferation of human neural stem/progenitor cells.
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.
Mori
Hideki
H
Research Institute for Cell Engineering, National Institute of Advanced Industrial Science and Technology, 3-11-46 Nakoji, Amagasaki, Hyogo 661-0974, Japan.
Kanemura
Yonehiro
Y
Onaya
Junichi
J
Hara
Masayuki
M
Miyake
Jun
J
Yamasaki
Mami
M
Kariya
Yutaka
Y
D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D006493:Heparin / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D006801:Humans; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*
D006493:Heparin