A.R. Møller (Ed.) Progress in Brain Research, Vol. 157 ISSN 0079-6123 Copyright r 2006 Elsevier B.V. All rights reserved CHAPTER 14 Novel cell therapy approaches for brain repair Svitlana Garbuzova-Davis 1,Ã , Alison E. Willing 1 , Samuel Saporta 1 , Paula C. Bickford 1 , Carmelina Gemma 1 , Ning Chen 1 , Cyndy D. Sanberg 3 , Stephen K. Klasko 2 , Cesario V. Borlongan 4 and Paul R. Sanberg 1 1 Center of Excellence for Aging and Brain Repair, Department of Neurosurgery, University of South Florida, College of Medicine, MDC 78, 12901 Bruce B. Downs Blvd., Tampa, FL 33612, USA 2 University of South Florida Health, 12901 Bruce B. Downs Blvd., Tampa, FL 33612, USA 3 Saneron CCEL Therapeutics Inc., 3802 Spectrum Blvd., Suite 145, Tampa, FL 33612, USA 4 Department of Neurology, Medical College of Georgia, 15th Street, Augusta, GA 30912, USA Abstract: Numerous reports elucidate that tissue-specific stem cells are phenotypically plastic and their differentiation pathways are not strictly delineated. Although the identity of all the epigenetic factors which may trigger stem cells to make a lineage selection are still unknown, the plasticity of adult stem cells opens new approaches for their application in the treatment of various disorders. There is increasing researcher interest in hematopoietic stem cells for treatment of not only blood-related diseases but also various unrelated disorders including neurodegenerative diseases. Human umbilical cord blood (hUCB) cells, due to their primitive nature and ability to develop into nonhematopoietic cells of various tissue lineages, including neural cells, may be useful as an alternative cell source for cell-based therapies requiring either the replacement of individual cell types and/or substitution of missing substances. Here we focus on recent findings showing the robustness of adult stem cells derived from hUCB and their potential as a source of transplant cells for the treatment of diseased or injured brains and spinal cords. Depending upon the pathological microenvironment in which the hUCB cells are introduced, neuroprotective and/or trophic effects of these cells, from release of various growth or anti-inflammatory factors to moderation of immune- inflammatory effectors, may be more likely than neural replacement. These protective effects may prove essential to maintaining restored tissue integrity over the course of various diseases or injuries. Keywords: neurodegenerative diseases; brain and spinal cord injury; umbilical cord blood cells; transplantation; alternative treatment Introduction The brain is a complex organ containing billions of neurons and other cells, specialized by structure and function. A unique cytoarchitecture and neu- ronal network of rigorous complexity compose the brain, the source of all the qualities that define our humanity. Since neurogenesis in the adult central nervous system (CNS) of all mammalians, includ- ing humans, was discovered (reviewed in Cameron and McKay, 1998; Gage, 2000; Gritti et al., 2002; Lie et al., 2004), the traditional view of the ina- bility of mature nervous tissues to renew and reconstruct themselves has been largely debunked. New neurons are constantly generated from neural stem cells throughout life in restricted brain regions which actually contain adult stem cells. These cells can give rise to differentiated progeny comprising the major cell types of the CNS, Ã Corresponding author. Tel.: (813) 974-3189; Fax: (813) 974- 3078; E-mail: sgarbuzo@health.usf.edu DOI: 10.1016/S0079-6123(06)57014-1 207