Abstract

Bone marrow stem cell therapies, based on transplant of hematopoietic stem cells (HSCs) have been used for over 50 years in the treatment of blood disorders including leukemia, lymphoma, and auto-immune disorders. Embryonic stem cells (ESCs) were discovered in the late 1990’s by Evans, Kauffman, and Martin. J Thompson developed procedures to isolate and expand ESCs from human embryos. Since ESCs could differentiate into any cell in the body, this expanded application of stem therapy to include broad areas in disease treatment and regenerative medicine. Use of ESCs was also associated with ethical/religious issues since their derivation from an embryo also destroyed the embryo. Recent research has shown that ESCs may form tumors following transplantation while adult stem cells have gained significant support for safety and efficacy in the treatment of skeletomuscular disorders and several other indications. Detailed studies have shown no evidence for malignant tumor formation from adult stem cell transplants. There are limitations of adult stem cell transplants including cost, potential safety issues, and the necessity of autologous transplants. Biological products activating endogenous HSCs have been used clinically in the treatment of anemia (recombinant human erythropoietin) and immuno-suppression (recombinant human G-CSF), resulting from chemotherapy for over 20 years. Recently, the endogenous cytokine BMP11 aka GDF11 has been shown to activate adult stem cells including Satellite muscle stem cells and possibly neural stem cells (NSCs). Additional studies have indicated that combined inhibition of GSK3-beta and HDAC-I may induce activation of NSCs, MSCs, and possibly other adult stem cell populations. We have developed a series of stem cell functional and activation assays measuring proliferation, migration, and epigenetic reprogramming. We describe initial results and validation data in this report. We also show that a new series of nutraceutical products, NutraVivo™ Dietary Supplements (Brain Grow Activator, Brain Grow Stimulator, and Brain Grow Energizer), activate human stem cells by these assays and from the performance of stem cells derived from a patient taking these nutraceuticals. Cell-based assays of stem cell function have application to quality control testing and development of new drug candidates.

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