Mobilization of human CD34⁺CD133⁺ and CD34⁺CD133⁻ stem cells in vivo by consumption of an extract from Aphanizomenon flos-aquae—related to modulation of CXCR4 expression by an L-selectin ligand?☆

Abstract 

Objective

The goal of this study was to evaluate effects on human stem cells in vitro and in vivo of an extract from the edible cyanobacterium Aphanizomenon flos-aquae (AFA) enriched for a novel ligand for human CD62L (L-selectin).

Experimental approach

Ligands for CD62L provide a mechanism for stem cell mobilization in conjunction with down-regulation of the CXCR4 chemokine receptor for stromal derived factor 1. Affinity immunoprecipitation was used to identify a novel ligand for CD62L from a water extract from AFA. The effects of AFA water extract on CD62L binding and CXCR4 expression was tested in vitro using human bone marrow CD34⁺ cells and the two progenitor cell lines, KG1a and K562. A double-blind randomized crossover study involving 12 healthy subjects evaluated the effects of consumption on stem cell mobilization in vivo.

Results

An AFA extract rich in the CD62L ligand reduced the fucoidan-mediated externalization of the CXCR4 chemokine receptor on bone marrow CD34⁺ cells by 30% and the CD62L⁺ CD34⁺ cell line KG1A by 50% but did not alter the CXCR4 expression levels on the CD34⁻ cell line K562. A transient, 18% increase in numbers of circulating CD34⁺ stem cells maximized 1 hour after consumption (P<.0003). When 3 noncompliant volunteers were removed from analysis, the increase in CD34⁺ cells was 25% (P<.0001).

Conclusion

AFA water extract contains a novel ligand for CD62L. It modulates CXCR4 expression on CD34⁺ bone marrow cells in vitro and triggers the mobilization of CD34⁺ CD133⁺ and CD34⁺ CD133⁻ cells in vivo.

Abbreviations: AFA, Aphanizomenon flos-aquae, PBMC, Peripheral blood mononuclear cells, PMN, Polymorph-nucleated cells

Keywords: L-selectin, Ligand, Human, Adult stem cell, CD34, CD133, KG1a, K562, Bone marrow, Mobilization, Blue-green algae, Cyanobacteria, Aphanizomenon, In vivo, In vitro