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?

Cardiovasc Revasc Med. Jul-Sep 2007;8(3):189-202. doi: 10.1016/j.carrev.2007.03.004.

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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • AC133 Antigen
  • Administration, Oral
  • Adult
  • Antigens, CD / analysis*
  • Antigens, CD34 / analysis*
  • Aphanizomenon / chemistry*
  • Capsules
  • Cell Extracts / administration & dosage
  • Cell Extracts / chemistry
  • Cell Extracts / pharmacology*
  • Cell Movement / drug effects*
  • Cells, Cultured
  • Cross-Over Studies
  • Double-Blind Method
  • Glycoproteins / analysis*
  • Humans
  • K562 Cells
  • L-Selectin / metabolism*
  • Ligands
  • Peptides / analysis*
  • Polysaccharides / metabolism
  • Receptors, CXCR4 / metabolism*
  • Stem Cells / drug effects*
  • Stem Cells / immunology
  • Stem Cells / metabolism

Substances

  • AC133 Antigen
  • Antigens, CD
  • Antigens, CD34
  • Capsules
  • Cell Extracts
  • Glycoproteins
  • Ligands
  • PROM1 protein, human
  • Peptides
  • Polysaccharides
  • Receptors, CXCR4
  • L-Selectin
  • fucoidan