Preparation of Neural Progenitors from Bone Marrow and Umbilical Cord Blood
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The ancient Chinese believed bone marrow was the source of brain tissue, as suggested by the maxim“Brain is a sea of marrow”
(1). The existence of stem cells for nonhematopoietic lineages in bone marrow was proposed over 100 years ago, but the isolation
and differentiation of marrow stromal cells into osteoblasts, chondroblasts, adipocytes, and myoblasts was only recently demonstrated
(2). Nonhematopoietic progenitors from bone marrow stroma have been referred to as colony-forming-unit (CFU) fibroblasts, mesenchymal
stem cells, or bone marrow stromal cells (BMSC). Although BMSC can naturally be expected to be a source of surrounding tissue
of bone, cartilage, and fat, several reports demonstrate that these cells, under specific experimental conditions, can differentiate
into muscle, glia, and hepatocytes (3–5). Most recently, BMSC have been shown to develop into cells that express proteins specific for neurons. The first documentation
of this phenomenon was performed in vitro (6). Human or rodent BMSC cultured in the presence of retinoic acid and epidermal growth factor (EGF) or brain-derived neurotrophic
factor (BDNF) expressed the mRNAs and proteins for nestin, neuron-specific nuclear protein (NeuN), and glial acidic fibrillary
protein (GFAP). When BMSC were co-cultured with rat fetal mesencephalic neurons, the proportion of BMSC that expressed neural
markers was increased (6). Another group of researchers reported that human BMSC could be induced to develop into neuron-like cells that express neuron-specific
enolase, NeuN, neurofilament-M, and tau following treatment with dimethylsulfoxide and butylated hydroxyanisole (7). The differentiation of BMSC into neurons was also demonstrated using two in vivo models. Intravenous delivery of genetically
marked adult BMSC into lethally irradiated normal adult hosts resulted in donor-derived cells expressing neuronal proteins
in the host brain (8). Another group demonstrated similar results, transplanting adult mouse BMSC into a strain of mice incapable of developing
cells of the myeloid and lymphoid lineages (9). These transplanted BMSC migrated into the brain and differentiated into cells that expressed neuron-specific antigens.
Taken together, these findings suggest that bone marrow-derived cells may provide an alternative source of neurons for treatment
of neurodegenerative diseases, trauma, and stroke.
Affiliation(s): (2) Department of Neurology and Center for Aging and Brain Repair, College of Medicine, University of South Florida, Tampa, FL
Book Title: Neural Stem Cells: Methods and Protocols
Series: Methods in Molecular Biology | Volume: 198 | Pub. Date: Feb-28-2002 | Page Range: 79-87 | DOI: 10.1385/1-59259-186-8:079
Subject: Cell Biology
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