Nutraceutical augmentation of circulating endothelial progenitor cells and hematopoietic stem cells in human subjects
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RESEARCH
Open Access
Nutraceutical augmentation of circulating endothelial progenitor cells and hematopoietic stem cells in human subjects Nina A Mikirova1,11, James A Jackson2,11, Ron Hunninghake2,11, Julian Kenyon3,11, Kyle WH Chan4,11, Cathy A Swindlehurst5,11, Boris Minev6,11, Amit N Patel7,11, Michael P Murphy8,11, Leonard Smith9,11, Famela Ramos9,11, Thomas E Ichim9,11*, Neil H Riordan1,9,10,11
Abstract The medical significance of circulating endothelial or hematopoietic progenitors is becoming increasing recognized. While therapeutic augmentation of circulating progenitor cells using G-CSF has resulted in promising preclinical and early clinical data for several degenerative conditions, this approach is limited by cost and inability to perform chronic administration. Stem-Kine is a food supplement that was previously reported to augment circulating EPC in a pilot study. Here we report a trial in 18 healthy volunteers administered Stem-Kine twice daily for a 2 week period. Significant increases in circulating CD133 and CD34 cells were observed at days 1, 2, 7, and 14 subsequent to initiation of administration, which correlated with increased hematopoietic progenitors as detected by the HALO assay. Augmentation of EPC numbers in circulation was detected by KDR-1/CD34 staining and colony forming assays. These data suggest Stem-Kine supplementation may be useful as a stimulator of reparative processes associated with mobilization of hematopoietic and endothelial progenitors. Introduction Autologous bone marrow derived stem cell therapy has demonstrated benefit in early clinical trials for conditions such as critical limb ischemia [1,2], post infarct remodeling [3], stroke [4,5], and liver failure [6]. While original mechanisms of action were believed to be associated with transdifferentiation of progenitor cells to injured tissues, more recent data supports the notion that trophic/paracrine mechanisms may be involved. In this scenario the primary therapeutic function of the administered cells is production of growth factors/antiapoptotic factors that accelerate tissue healing [7-9]. Unfortunately, despite our more advanced mechanistic understanding of cellular therapy, its widespread implementation is hindered by need for complex cell processing facilities that are only available at limited medical institutions. A more simplistic strategy would involve administration of agents capable of enhancing endogenous stem cell activity, or alternatively mobilizing bone
* Correspondence: [email protected] 9 Medistem Inc, San Diego, California, USA
marrow resident stem cells to increase concentration to an area of need. It is known that subsequent to a variety of tissue injuries, such as myocardial infarction [10], stroke [11], and long bone fractures [12,13], endogenous stem cells are mobilized to the periphery, en route to the site of damage. The cytokines stromal derived factor (SDF-1) [10], vascular endothelial growth factor (VEGF) [14], and hepatocyte growth factor (HGF-1) [15] appear to act as homing signal
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