Current Neurovascular Research, 2004, 1, 000-000 1 1567-2026/04 $45.00+.00 ©2004 Bentham Science Publishers Ltd. Use of Human Umbilical Cord Blood (HUCB) Cells to Repair the Damaged Brain Mary B. Newman 1,2,3 , Dwaine F. Emrich 1 , Cesario V. Borlongan 8-11 , Cyndy D. Davis Senberg 7 and Paul R. Sanberg 1-7, * 1 Center of Excellence for Aging and Brain Repair, 2 Departments of Neurosurgery, 3 Psychology, 4 Psychiatry, 5 Pathology and 6 Pharmacology, 7 University of South Florida, College of Medicine, Tampa FL 33612, 7 Saneron CCEL Therapeutics, Inc., Tampa, FL 33637, 8 Department of Neurology, 9 Institute of Molecular Medicine and Genetics, School of Graduate Studies, 10 Medical College of Georgia, Research and Affiliations Service Line, 11 Augusta Veterans Administration Medical Center, Augusta GA 30912 Abstract: Neurodegenerative diseases as well as acute center nervous system (CNS) injuries remains a problematic and frustrating area of medicine in terms of treatments and cures, which is mostly due to the complex circuitry of the CNS along with our limited knowledge. Therapeutically, the last two and a half decades have offered new hope for those suffering from neurodegenerative diseases or injuries with advent of new drug discoveries and cellular therapies. Cell transplantation is a compelling and potential treatment for certain neurological and neurodegenerative diseases as well as for acute injuries to the spinal cord and brain. The hematopoietic system offers an alternative source of cells that is easily obtainable, abundant, and reliable when compared to cells obtained from fetal or embryonic origins. Human umbilical cord blood (HUCB) cells have been used clinically for over ten years to treat both malignant and non-malignant diseases. With in the last five years these cells have been used pre-clinically in animal models of brain and spinal cord injuries, in which functional recovery have been shown. This paper reviews the advantages, utilization, and progress of HUCB cells in the field of cellular transplantation and repair. Key Words: Human umbilical cord blood cells, neurodegeneration, neural stem cells, cell replacement, traumatic brain injury, spinal cord injury, ALS, transplantation, neural and neuronal phenotypes, immunocytochemistry, stroke, ischemia, middle cerebral artery occlusion (MCAO), and behavior. INTRODUCTION Numerous CNS diseases are characterized by the deter- ioration of cognitive and motor functions frequently leading to prolonged periods of increasing incapacity. Among the most problematic and prevalent neurological disorders are those associated with the loss of varying populations of CNS cells, such as Alzheimer’s (AD), Parkinson’s (PD), and Huntington’s disease (HD), amyotropic lateral scelerosis (ALS), and stroke. While advances in molecular biology, genetic engineering, proteomics, and genomics will produce compounds with enormous treatment potential in the future, currently there are no available means of altering the pattern, rate of cell loss, or function in diseased or injured CNS once damage has occurred. For several decades, researchers and clinicians have been exploring the potential of cellular treatment for diseases, disorders, and injures of the CNS. Fetal neural tissue was initially grafted into the brain in order to study its develop- ment and regenerative capacity. These studies quickly revealed the therapeutic potential of tissue grafting in animal models of neurological disorders, which eventually led to pre-clinical and then clinical trials. The outcomes of clinical *Address Correspondence to this Author at the University of South, College of Medicine MDC-78, Center of Excellence for Aging and Brain Repair, Tampa, Fl 33612, USA; Tel: 813-974-3154; E-mail: psanberg@hsc.usf.edu Received: 09/10/03; Revised: 02/10/04; Accepted: 02/15/04 transplantation studies were generally positive enough to warrant further investigation. However, the lack of signifi- cant improvement reported in the older population or late stage of disease in patients with Parkinson’s disease has bought some doubt and uncertainty to the future direction of the neural transplantation field (Newman, Freeman, Davis, & Sanberg, 2003; Sanberg, Willing, & Cahill, 2002). In addition, societal, legal, and ethical issues, along with the limited availability of tissue, complicate the use of fetal tissue. These factors have not only urged investigators to look for alternative sources of cells, but also alternative way in which cells may be utilized in cellular therapies. This is supported by the growing consensus that stem cells are obtainable from several sources and can be epigenetically expanded or genetically perpetuated to develop, if needed, into specific cellular phenotypes or to deliver needed subs- trates/factors from genetically engineered cells. One of the most promising sources for human stem cells are those cells from hematopoietic origin, which include human umbilical cord blood (HUCB), adult peripheral blood, and bone marrow. Each have their own sets of distinct advantages and disadvantages and it is beyond the scope of this article to adequately discuss each. Rather, this review focuses on the utilization of HUCB cells as a potential source for cellular therapies. Stem cells derived from hematopoietic sources, such as HUCB, is an emerging and relatively young field of