Clinical haemopoietic implications of fucoidan treatment

Haematopoiesis is a term that describes the formation of mature cellular blood components from haemopoietic progenitor stem cells (HPC). The majority of HPC reside in the bone marrow (BM) with a small number continually escaping into the circulation then re-homing back into the BM in a process called trafficking. Stromal cells in the BM constitutively express and secrete stromal cell derived factor (SDF-1). This highly conserved chemokine binds to heparin and to CXCR4 receptor acting as a chemo-attractant for CXCR4\\(^+\\) cells; the system plays a role in regulating stem cell trafficking. This study examined the clinical effects of ingesting fucoidan extracted from brown macro-algae (Undaria pinnatifida) in vitro and in vivo in a series of single blinded placebo-controlled clinical trials. Fucoidans comprise sulphated long branched chains of sugar, containing large amounts of fucose and galactose. Fucoidan is biologically active and is known to modulate coagulation, inflammation, cell proliferation and adhesion, tumorigenesis and resistance to viral infection. To study its clinical value an ELISA assay based on a novel antibody was established to quantify the level of the bio-available fucoidan in human plasma after oral doses. The consequences of ingesting fucoidan on healthy volunteers were investigated in detail by studying different biological and pathological parameters including liver and kidney functions. This study established that daily ingestion of 3 g of different fucoidan extracts for 2 weeks is safe. To study the anticoagulant activity of fucoidan, haemostasis was examined closely in vitro and in vivo. Although, fucoidan is a highly potent anticoagulant in vitro there was limited activity when used orally. Fucoidan was found also to positively regulate the lipid profile by reducing cholesterol and triglyceride plasma levels. The effect of fucoidan on HSPC trafficking was tested. Ingestion of fucoidan increased the expression of CXCR4 on CD34\\(^+\\) cells and increased the plasma level of SDF-1 and IFN-˜í‚â•. A decrease in CD4\\(^+\\) and CD8\\(^+\\)+ cells was also observed in volunteers who ingested fucoidan. When either peripheral blood or cord blood CD34+ cells were cultured in vitro in a cytokine expansion system CXCR4 on CD34\\(^+\\) cells was down-regulated. This study also showed that fucoidan slows down the CD34\\(^+\\) cell cycle and interacts and binds with different cytokines (SCF, TPO, Flt-3 and SDF-1) and presents them to cells. In conclusion, this study showed that fucoidan has several clinical effects including effects on lipids regulation, haemostasis, immune system, haematopoiesis, trafficking of HSPC and related cytokines.