Transplantation of hematopoietic progenitor stem cells (HPC) is a treatment that aims to completely cure blood cancers, including immunodeficiency diseases that are difficult to cure with ordinary chemotherapy and immunosuppressive therapy alone.

In hematopoietic stem cell transplantation, hematopoietic stem cells are collected in advance from the patient or a donor. Then, they are administered by intravenous drip after a pre-transplant treatment consisting of high-dose chemotherapy or whole-body radiation therapy. Cancers such as blood and lymphatic cancers that are easily treated with chemotherapy and radiotherapy are targeted for treatment. Still, there are cases known to have strong side effects and complications compared to conventional treatment methods.

On a positive note, there have been studies on fucoidan benefits. Fucoidan does not have side effects, and it is possible to regulate the hematopoietic stem and progenitor cell (HSPC) function. However, there are no reports about the clinical use of oral fucoidan to modulate or mobilize HPC.

Hence, in this blog, I would like to share the study “Fucoidan ingestion increases the expression of CXCR4 on human CD34þ cells” by Mohammad R. Irhimeh et al.

In this study, they investigated the effects of oral intake of Undaria pinnatifida fucoidan on PB stem cells, expression of CXCR4, plasma levels of SDF-1, IL-12, and IFN-g.

HPCs can be recruited from the bone marrow (BM) niche to peripheral blood (PB) via the administration of granulocyte colony-stimulating factor (G-CSF) or other agents such as AMD3100 or fucoidan.

Subsequent engraftment success may be associated with the expression of the receptor CXCR4 that critically regulates the hematopoietic stem and progenitor cell (HSPC) function on CD34 (a Protein Coding gene) + HPCs. This effect can be observed both clinically and experimentally. However, recruitment of adequate amounts of HPCs containing CD34þ CXCR4þ is not always successful. Adequate mobilization may not be achieved in patients who received multiple cycles of chemotherapy or for other unknown reasons.

On the other hand, Fucoidan intake has an inhibitory effect on tumors that appears to be associated with increased interferon-gamma (IFN-g), interleukin-12 (IL-12), and stimulation of natural immunity.

The study further investigated the effects of orally ingested Undaria pinnatifida fucoidan on PB stem cells, CXCR4 expression, and plasma levels of SDF-1, IL-12, and IFN-g.

First, thirty-seven nonsmoker volunteers of either sex were divided into three groups. As a placebo, six volunteers received 3 g of guar gum. Another of her six volunteers took 3 g of whole Undaria containing 10% w/w fucoidan, and another of 25 volunteers took 3 g of her 75% w/w. Each volunteer daily took three fucoidan capsules (0.33 g each) 3 times a day for 12 days.

As a result, no side effects were reported. In addition, none of the volunteers demonstrated toxicity when 3 g of guar gum, 10% fucoidan, or 75% fucoidan extract were taken orally three times daily for 12 days. Fucoidan intake caused mild leukopenia and lymphopenia but did not affect neutrophils.

A non-significant reduction in the number of white blood cells in PB was observed when fucoidan was added at 10%. However, when 75% fucoidan was taken, it decreased significantly after 12 days.

A slight increase in circulating CD34þ was also observed after fucoidan intake. Ingestion of 10% fucoidan (3 g/d) non-significantly increased CD34+ in PB from 1.07 to 1.29 cells/mL (p 5 0.06, n 5 6) after 12 days; however, with 75% fucoidan intake, the CD34+ count increased from 1.64 cells/mL to 1.84, 1.80, and 1.79 cells/mL at 4, 8, and 12 days, respectively. (See Figure -1)

As the experiment in vitro, the binding of L-selectin to lymphocytes by fucoidan enhanced CXCR4 expression in lymphocytes. Moreover, assessing plasma levels of IFN-g is associated with the upregulation of CXCR4—a significant increase in plasma of volunteers ingesting 3g of 75% fucoidan (p 5 0.04).

Also, average numbers of functional neutrophils must be critical for HPC recruitment. This study established that 3g of oral fucoidan did not affect neutrophil counts and did not cause neutropenia. And in their studies, the level of SDF-1, IFN-g, and IL-12 did not change.

As a result, oral fucoidan significantly amplified the CXCR4+ HPC population. The ability to mobilize HPCs using sulfated polysaccharides and more HPCs with high levels of CXCR4 may be of clinical value. However, the effects of IV fucoidans in humans have not yet been determined. Further research is needed.