REJUVENATION RESEARCH Volume 10, Number 2, 2007 © Mary Ann Liebert, Inc. DOI: 10.1089/rej.2006.0515 Oxidative Stress of Neural, Hematopoietic, and Stem Cells: Protection by Natural Compounds 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. Bickford 1,3 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 it- self. 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 con- ducting a clinical trial to determine if NT020 exhibits similar health promoting effects in hu- mans when used as a dietary supplement. 173 INTRODUCTION A STEM CELL IS A SPECIAL KIND of cell that has a unique capacity to renew itself and to give rise to specialized cell types. These cells are found in many organs of the adult human including bone marrow, peripheral blood, um- bilical cord blood, spleen, tooth pulp, adipose tissue, and brain. Stem cell research is currently a popular subject in the media and science. 1 While stem cell therapies have been promised to offer important new treatments for a wide variety of illnesses, there are two primary ob- stacles to their ultimate success. First, stem cell therapies remain controversial due to the focus on fetal derived embryonic stem cells. Second, stem cell therapies may take many years to reach the medical market place because of the lengthy and costly regulatory requirements. Fortunately, a growing body of evidence suggests that there are numerous stem cells continually being produced within the human body throughout the lifespan. These stem cells are located in many different tissues and can become or “differentiate” into virtually any cell type in the body. Internal or “endogenous” stem cells are crucial to the body’s ability to re- pair itself of degenerating tissues, or to replace cell populations, such as those that have been destroyed by injuries, diseases, disorders, or treatments such as chemotherapy. Healthy stem cells are vital for the body’s own natural regeneration and repair mechanisms to func- tion. During natural aging, adult stem cells are known to have a reduced restorative capacity 2 and are more vulnerable to oxidative stress 3 re- sulting in a reduced ability of the body to heal 1 Center of Excellence for Aging and Brain Repair, Department of Neurosurgery, 2 Silver Child Development Cen- ter, Department of Psychiatry, University of South Florida College of Medicine, 3 James A Haley Veterans Adminis- tration Hospital, 4 Natura Therapeutics, Inc., Tampa, Florida.