Preparation of Neural Progenitors from Bone Marrow and Umbilical Cord Blood
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, 4, 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.
KeywordsBone Marrow Stromal Cell Butylate Hydroxyanisole Neural Precursor Cell Normal Horse Serum Human Umbilical Cord Blood
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