Stem Cells and Progenitors in Human Peripheral Blood Get Activated by Extremely Active Resveratrol (XAR™)

Abstract

Resveratrol generated enormous interest as it improved functions of multiple organs and could delay aging in animal models. However, basic mechanism of action was not understood and due to poor bioavailability, it has failed to enter the market. A highly active nano-formulation of resveratrol (XAR™) with enhanced bioavailability is now available. Present study was undertaken to evaluate its effects on stem cells biology in the human peripheral blood. Twelve healthy participants were enrolled of which five received XAR™, five were age-matched placebo controls and two were 76 and 85 years old. Peripheral blood was processed to study serum profile to monitor cardiac and pancreatic functions and subjected to density gradient centrifugation to enrich pluripotent (VSELs) and adult stem cells that get enriched along with red blood cells and in the Buffy coat respectively on Day 2 and Day 15 after XAR™ treatment. The XAR™ treatment resulted in an increased expression of pluripotency transcripts specific for VSELs (Oct-4A, Nanog and Sox2) on D2; specific transcripts for differentiation in the progenitors including Oct-4, Ikaros, CD14, CD90 on D15, and anti-ageing and tumor suppressor transcripts NAD, SIRT1, SIRT6 and p53 in both stem cells and progenitors. An improvement of cardiac and pancreatic markers in serum profile was also observed on D15. The decline in VSELs numbers with age and beneficial effects of the XAR™ treatment were evident by up-regulation of specific transcripts and on serum profile. XAR™ is a promising molecule that has the potential to activate pluripotent VSELs and tissue committed adult stem cells 'progenitors' resulting in the rejuvenation of various body tissues and for improved, cancer-free health with advanced age.

RETRACTED ARTICLE: Extremely Active Nano-formulation of Resveratrol (XAR™) attenuates and reverses chemotherapy-induced damage in mice ovaries and testes

“…We have earlier reported a direct action of XAR ™ on stem cells in human blood [22]. The tissue-resident VSELs express pluripotent markers along with ERα, ERβ and FSHR in multiple tissues [23,24] and thus it was of interest to study if XAR ™ could exert similar effects like FSH on the ovaries.…”

Similar Population of CD133+ and DDX4+ VSEL-Like Stem Cells Sorted from Human Embryonic Stem Cell, Ovarian, and Ovarian Cancer Ascites Cell Cultures: The Real Embryonic Stem Cells?

“…A population of small stem cells showing pluripotency persists from the embryonic period of life in adult human tissues and organs, such as bone marrow, umbilical cord blood and peripheral blood, and are termed very small embryonic-like stem cells (VSELs). These cells were first discovered by the research group of Ratajczak [1,2] and further explored by several other groups in bone marrow [3,4,5,6,7,8], umbilical cord blood [9,10,11,12], peripheral blood [13,14], uterine endometrium [15], testis [16], retina [17] and bone [18] in humans and rodents. VSELs are proposed to originate in the embryonic epiblast during development [19,20], mobilized into the peripheral blood under inappropriate conditions (e.g., stroke, myocardial ischaemia, skin burn injury, septic shock, brain injury, Crohn’s disease) to regenerate the tissues and organs [21,22,23,24,25,26], and proposed to be able to regenerate organs, such as the pancreas, brain, lung, liver or heart, by transplantation [27,28,29,30,31].…”

Resveratrol-related compounds: Potential for cancer and beyond

“…The fact that RV's beneficial effects may depend on reaching a specific in vivo concentration, points to the need for a better controlled pharmacological profile to achieve the desired effects (Scott et al, 2012;Cai et al, 2015). Better RV bioavailability is under active investigation (Chimento et al, 2019), including via alternative formulations (Howells et al, 2011;Tripathi et al, 2018), nano-encapsulation to assist the delivery and release (Santos et al, 2019) and chemical analogues including hydroxylated (Piotrowska et al, 2012) or methylated (Kapetanovic et al, 2011) derivatives such as pterostilbene showing superior bioavailability in vivo. One derivative in particular, trans-4,4′-dihydroxystilbene or DHS has shown promising biological characteristics.…”