The research articles in their entirety are available for purchase from Simplexity Health. The research was done using the ingredients in the base formula included in Simplexity Health's StemPlex. Our formula includes Aphanizomenon flos-aquae; preliminary data (not yet published) indicates that even better results are expected with the inclusion of Aphanizomenon flos-aquae.

Paula C. Bickford, 1,2 Jun Tan, 1 R. Douglas Shytle, 1 Cyndy D. Sanberg, 3 Nagwa El-Badri, 1 and Paul R. Sanberg 1

ABSTRACT
A viable alternative to stem cell transplantation is to design approaches that stimulate endogenous stem cells to promote healing and regenerative medicine. Many natural compounds have been shown to promote healing; however, the effects of these compounds on stem cells have not been investigated. We report here the effects of several natural compounds on the proliferation of human bone marrow and human CD34+ and CD133+ cells. A dose-related effect of blueberry, green tea, catechin, carnosine, and vitamin D3 was observed on proliferation with human bone marrow as compared with human granulocyte-macrophage colony-stimulating factor (hGM-CSF). We further show that combinations of nutrients produce a synergistic effect to promote proliferation of human hematopoietic progenitors. This demonstrates that nutrients can act to promote healing via an interaction with stem cell populations.

STEM CELLS AND DEVELOPMENT 15:118-123 (2006)
© Mary Ann Liebert, Inc.

R. Douglas Shytle,1 Jared Ehrhart,2 Jun Tan,1,2 Jennifer Vila,1 Michael Cole,1 Cyndy D. Sanberg,4 Paul R. Sanberg,1 and Paula C. Bickford1,3

ABSTRACT
During natural aging, adult stem cells are known to have a reduced restorative capacity and are more vulnerable to oxidative stress resulting in a reduced ability of the body to heal itself. We report here that the proprietary natural product formulation, NT020, previously found to promote proliferation of human hematopoietic stem cells, reduced oxidative stress-induced apoptosis of murine neurons and microglial cells in vitro. Furthermore, when taken orally for 2 weeks, cultured bone marrow stem cells from these mice exhibited a dose-related reduction of oxidative stress-induced apoptosis. This preclinical study demonstrates that NT020 can act to promote healing via an interaction with stem cell populations and forms the basis of conducting a clinical trial to determine if NT020 exhibits similar health promoting effects in humans when used as a dietary supplement.

REJUVENATION RESEARCH
Volume 10, Number 2, 2007
© Mary Ann Liebert, Inc.
DOI: 10.1089/rej.2006.0515

Takao Yasuhara,¹ Koichi Hara,¹ Mina Maki,¹ Tadashi Masuda,¹ Cyndy D. Sanberg,² Paul R. Sanberg,³ Paula C. Bickford,^3,4 and Cesar V. Borlongan ^1,5

ABSTRACT
This study examined whether dietary supplementation can be used to protect against ischemic stroke. Two groups of adult male Sprague-Dawley rats initially received NT-020, a proprietary formulation of blueberry, green tea, vitamin D3, and carnosine (n=8), or vehicle (n=7). Dosing for NT-020 and vehicle consisted of daily oral administration (using a gavage) over a 2-week period. On day 14 following the last drug treatment, all animals underwent the stroke surgery using the transient 1-hour suture occlusion of middle cerebral artery (MCAo). To reveal the functional effects of NT-020, animals were subjected to established behavioral tests just prior to stroke surgery and again on day 14 post-stroke. ANOVA revealed significant treatment effects (pô°0.05), characterized by reductions of 11.8% and 24.4% in motor asymmetry and neurologic dysfunction, respectively, in NT-020-treated stroke animals compared to vehicle-treated stroke animals. Evaluation of cerebral infarction revealed a significant 75% decrement in mean glial scar area in the ischemic striatum of NT-020-treated stroke animals compared to that of vehicle-treated stroke animals (p < 0.0005). Quantitative analysis of subventricular zone's cell proliferative activity revealed at least a one-fold increment in the number of BrdU-positive cells in the NT-020-treated stroke brains compared to vehicle-treated stroke brains (p < 0.0005). Similarly, quantitative analysis of BrdU labeling in the ischemic striatal penumbra revealed at least a three-fold increase in the number of BrdU- positive cells in the NT-020-treated stroke brains compared to vehicle-treated stroke brains (p < 0.0001). In addition, widespread double labeling of cells with BrdU and doublecortin was detected in NT-020-treated stroke brains (intact side 17% and ischemic side 75%), which was significantly higher than those seen in vehicle-treated stroke brains (intact side 5% and ischemic side 13%) (p < 0.05). In contrast, only a small number of cells in NT-020-treated stroke brains double labeled with BrdU and GFAP (intact side 1% and ischemic side 2%), which was significantly lower than those vehicle-treated stroke brains (intact side 18% and ischemic side 35%) (p < 0.0001). Endogenous neurogenic factors were also significantly upregulated in the ischemic brains of NT-020-treated stroke animals. These data demonstrate the remarkable neuroprotective effects of NT-020 when given prior to stroke, possibly acting via its neurogenic potential.

REJUVENATION RESEARCH
Volume 11, Number 1, 2008
© Mary Ann Liebert, Inc.
DOI: 10.1089/rej.2007.0608

¹ Department of Neurology, Medical College of Georgia, Augusta, Georgia.
² Natura Therapeutics, Inc., Tampa, Florida.
³ Center of Excellence for Aging and Brain Repair, Department of Neurosurgery, University of South Florida College of Medicine, Tampa, Florida.
⁴ James A. Haley Veterans Administration Hospital, Tampa, Florida.
⁵ Research and Affiliations Service Line, Augusta VAMC, Augusta, Georgia.

Douglas Shytle, Jun Tan, Jared Ehrhart, Adam Smith, Cyndy Sanberg, Paul Sanberg, Jerry Anderson, Paula Bickford

ABSTRACT
Adult stem cells are known to have a reduced restorative capacity as we age and are more vulnerable to oxidative stress resulting in a reduced ability of the body to heal itself. We have previously reported that a proprietary nutraceutical formulation, NT-020, promotes proliferation of human hematopoietic stem cells in vitro and protects stem cells from oxidative stress when given chronically to mice in vivo. Because previous reports suggest that the blue green algae, Aphanizomenon flos-aquae (AFA) can modulate immune function in animals, we sought to investigate the effects of AFA on human stem cells in cultures. Two AFA products were used for extraction: AFA whole (AFA-W) and AFA cellular concentrate (AFA-C). Water and ethanol extractions were performed to isolate active compounds for cell culture experiments. For cell proliferation analysis, human bone marrow cells or human CD34+ cells were cultured in 96 well plates and treated for 72 hours with various extracts. An MTT assay was used to estimate cell proliferation. We report here that the addition of an ethanol extract of AFA-cellular concentrate further enhances the stem cell proliferative action of NT-020 when incubated with human adult bone marrow cells or human CD34+ hematopoietic progenitors in culture. Algae extracts alone had only moderate activity in these stem cell proliferation assays. This preliminary study suggests that NT-020 plus the ethanol extract of AFA cellular concentrate may act to promote proliferation of human stem cell populations.

Med Sci Monit 2010; 16(1): BR 1 – 5

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