Cellular therapy is a compelling and potential treat- ment for certain neurological and neurodegenera- tive diseases as well as a viable treatment for acute injury to the spinal cord and brain. The hematopoi- etic system offers alternative sources for stem cells compared to those of fetal or embryonic origin. Bone marrow stromal and umbilical cord cells have been used in pre-clinical models of brain injury, directed to differentiate into neural phenotypes, and have been related to functional recovery after engraftment in central nervous system (CNS) injury models. This paper reviews the advantages, utiliza- tion and progress of human umbilical cord blood (HUCB) cells in the neural cell transplantation and repairfield. Keywords: Human umbilical cord blood; Neural cell trans- plantation; Central nervous system; Hematopoietic cells; Stem cells INTRODUCTION Cell replacement/repair therapy is a growing and piv- otal area of scientific research. Although cell transplan- tation has made tremendous progress in the last 20 years, there have been negative aspects reported from clinical trials. In addition, the ethical concerns involv- ing the use of fetal cells or tissue and preserved embry- onic stem cells accompanied by their limited availabil- ity has overshadowed, and in some instances, delayed progress in the cell transplantation field. With the surge of findings that various sources of stem cells may be directed by either epigenetic expansion or genetic per- petuation to certain phenotypes, the search for human cells that are of non-fetal origin that contain stem cells is at the forefront of the cell transplantation and repair field. Two possible candidates for potential stem cells come from hematopoietic sources and are those from HUCB and bone marrow. Two excellent review articles have discussed the use of bone marrow cells as source for neural stem cells for transplantation (Sanchez- Ramos et al. , 2000; Sanchez-Ramos, 2002). This arti- cle will focus on the existence of stem cells within and the advantages of HUCB, studies that have reported neural phenotypes of these cells both in vitr o and in vivo , and transplantation studies that have used HUCB in injured, diseased, or neurodegenerative animal mod- els. Brief History of Stem Cells Most stem cell biologists would agree that Artur Pappenheim (1870-1916) was the first to propose the concept of a common ancestral stem cell (Lajtha, 1980). Till and McCulloch (1961) were the first to demonstrate the ability of transplanted bone marrow cells to form colony-forming units (CFU) on the spleen of lethally irradiated mice. Their initial studies meas- ured the proliferation potential of bone marrow cell colonies, and led to the developing hypothesis of hematopoietic stem cells (Potten, 1983; Till and McCulloch, 1961). Since then much confusion has occurred in the meaning and usage of the words "stem, progenitor, and precursor cells." In an attempt to unify terminology in this field, a workshop in 1978 comprised mostly of hematologists (Lajtha, 1979), defined stem cells as "cells with exten- sive self-maintaining (self-renewal capacity), extend- ing throughout the whole (or most) of the life-span of Human Umbilical Cord Blood (HUCB) Cells for Central Nervous System Repair MARY B. NEWMAN a, *, CYNDY D. DAVIS b , NICOLE KUZMIN-NICHOLS b , and PAUL R. SANBERG a a Center of Excellence for Aging and Brain Repair, Departments of Neurosurgery , Psychology , Psychiatry , Neurology, Pathology and Pharmacology , University of South Florida, College of Medicine, Tampa FL 33612, USA; and b Saneron CCEL Therapeutics, Inc., Tampa, FL 33637, USA. (Received 28 April 2003; Revised 02 June 2003; In final form 02 June 2003) *Corresponding author . ISSN 1029 8428 print/ ISSN 1476-3524 online. © 2003 FP Graham Publishing Co., www.fpgrahamco.com F.P. Graham Publishing Co. G h P bli hi C Neurotoxicity Research, 2003, VOL. 5(5). pp. 355-368