Neural Stem-like Cell Line Derived from a Nonhematopoietic Population of Human Umbilical Cord Blood

Abstract

The ability of stem and progenitor cells to proliferate and differentiate into other lineages is widely viewed as a characteristic of stem cells. Previously, we have reported that cells from a CD34(-) (nonhematopoietic) adherent subpopulation of human cord blood can acquire a feature of multipotential neural progenitors in vitro. In the present study, using these cord blood-derived stem cells, we have established a clonal cell line termed HUCB-NSCs (human umbilical cord blood-neural stem cells) that expresses several neural antigens and has been grown in culture for more than 60 passages. During this time, HUCB-NSCs retained their growth rate, the ability to differentiate into neuronal-, astrocyte-, and oligodendrocyte-like cells and displayed a stable karyotype. DNA microarray analysis of HUCB-NSCs revealed enhanced expression of selected genes encoding putative stem and progenitor cell markers when compared to other mononuclear cells. dBcAMP-induced HUCBNSCs were further differentiated into more advanced neuronal cells. This is the first report of the establishment and characterization of a nontransformed HUCB-NSC line that can be grown continuously in a monolayer culture and induced to terminal differentiation. These cells should further our understanding of the regulatory mechanisms involved in NSC self-renewal and differentiation.

Long-term cultured human umbilical cord neural-like cells transplanted into the striatum of NOD SCID mice

“…These cells could potentially be included in our cell culture since we do not remove the non-hematopoietic cells. Since the number of CD45+ cells was reduced in our long-term culture, this suggests that our long-term culture could be transforming into the neural stemlike line detected by Buzanska et al [3].…”

“…Recent studies demonstrate that long-term culture of HUCB enhanced neural content of cell cultures (Jurga et al [24]; an observation which we also see), however, Jain et al [21] saw an overall decrease in neuronal number with long-term culture, but an increased migration of cells with a neuronal phenotype (but not of total cells) in the hippocampus in intact rat brain. Buzanska et al [3] have also generated a neural stem-like line from the non-hematopoietic fraction of HUCB. These cells could potentially be included in our cell culture since we do not remove the non-hematopoietic cells.…”

Rescuing the neonatal brain from hypoxic injury with autologous cord blood

“…[66][67][68][69][70] Cell lines with NSC properties have been established from HUCB following immune-depletion of the CD34-positive cells from CB and spontaneous aggregation and differentiation with stimulation by epithelial growth factor. 71 When such CB-NSCs were seeded on human-originated biodegradable scaffold, they were able to differentiate into neurons, form functional circuits and generate spontaneous field/action potentials. 72 Recently, Tracy et al 73 demonstrated that oligodendrocyte progenitors could also be isolated and expanded ex vivo from human CB.…”

A novel, neural potential of non-hematopoietic human umbilical cord blood stem cells

“…HUCB has a good chance of becoming the ideal source for such standardized transplantable material. Our laboratory has successfully derived a non-immortalized cell-line with properties of neural stem cells (Buzanska et al, 2003;Buzanska et al, 2006b). This cell line of HUCB-NSCs serves as a useful prototype for the ideal transplantable material depicted above, and, upon sufficient characterization in animal models, it has a strong potential for clinical use.…”

“…The first (Buzanska et al, 2001a) and then published in 2002 (Buzanska et al, 2002). Thereafter, through repeated passages of floating, round-shaped, nestin-positive and clonogenic cells from these neural progenitors population we have established the first, expanding, indefinitely growing HUCB-NSC cell line (Buzanska et al, 2003;Buzanska et al, 2006b). …”