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?
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.
STEMTech HealthSciences, Inc., San Clemente, CA, USA. cdrapeau@stemtechmail.com
Abstract
Bone marrow-derived stem cells have the ability to migrate to sites of tissue damage and participate in tissue regeneration. The number of circulating stem cells has been shown to be a key parameter in this process. Therefore, stimulating the mobilization of bone marrow stem cells may accelerate tissue regeneration in various animal models of injury. In this study we investigated the effect of the bone marrow stem cells mobilizer StemEnhance (SE), a water-soluble extract of the cyanophyta Aphanizomenon flos-aquae (AFA), on hematopoietic recovery after myeloablation as well as recovery from cardiotoxin-induced injury of the anterior tibialis muscle in mice. Control and SE-treated female mice were irradiated, and then transplanted with GFP(+) bone marrow stem cells and allowed to recover. Immediately after transplant, animals were gavaged daily with 300 mg/kg of SE in PBS or a PBS control. After hematopoietic recovery (23 days), mice were injected with cardiotoxin in the anterior tibialis muscle. Five weeks later, the anterior tibialis muscles were analyzed for incorporation of GFP(+) bone marrow-derived cells using fluorescence imaging. SE significantly enhanced recovery from cardiotoxin-injury. However, StemEnhance did not affect the growth of the animal and did not affect hematopoietic recovery after myeloablation, when compared to control. This study suggests that inducing mobilization of stem cells from the bone marrow is a strategy for muscle regeneration.
Method for enhancing stemcell trafficking US 8034328 B2
AFA萃取物能提升血液中幹細胞濃度
Consumption of blue-green algae, or extracts thereof, enhances trafficking or homing of stem cells in animals by inducing a transient increase in the population of stem cells present in the animal's circulatory system. The animal may be healthy or suffering some disease or physiological condition.
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