Region-specific generation of cholinergic neurons from fetal human neural stem cells grafted in adult rat

Abstract

Pluripotent or multipotent stem cells isolated from human embryos or adult central nervous system (CNS) may provide new neurons to ameliorate neural disorders. A major obstacle, however, is that the majority of such cells do not differentiate into neurons when grafted into non-neurogenic areas of the adult CNS. Here we report a new in vitro priming procedure that generates a nearly pure population of neurons from fetal human neural stem cells (hNSCs) transplanted into adult rat CNS. Furthermore, the grafted cells differentiated by acquiring a cholinergic phenotype in a region-specific manner. This technology may advance stem cell-based therapy to replace lost neurons in neural injury or neurodegenerative disorders.

Compatibility of human fetal neural stem cells with hydrogel biomaterials in vitro

“…This allows us to obtain neurons when the primed hNSCs are grafted into non-neurogenic areas in adult rats (Wu et al, 2002;Tarasenko et al, 2007). Collecting primed cells and embedding them within the hydrogels would most appropriately mimic the environment that the cells would experience post-transplantation.…”

“…These cells proliferate in vitro in neurospheres, which consist of a heterogeneous population of neural stem cells and neural progenitors (Suslov et al, 2002). We have previously shown that mitogen-expanded and primed (Wu et al, 2002;Tarasenko et al, 2004) hNSCs become cholinergic motoneurons when grafted into acutely or chronically injured rat spinal cords (Gao et al, 2005;Tarasenko et al, 2007). However, grafted hNSCs showed limited survival rates and migrational capabilities within the injured cavity indicating the need for a scaffold support.…”

Isolation and Characterization of Tumorigenic, Stem-like Neural Precursors from Human Glioblastoma

“…This provides a stringent, low-density system (Ͻ5 ϫ 10 3 cells/cm 2 ), which selects away differentiated/ differentiating cells in primary CNS cultures, leaving neural stem cells free to proliferate and expand exponentially (25,26).…”

Overexpression of Basic Helix-Loop-Helix Transcription Factors Enhances Neuronal Differentiation of Fetal Human Neural Progenitor Cells in Various Ways

“…Finally, Ngn2, Ngn3, and Mash1 had no effect on adrenergic and serotoninergic neuron production, whereas Ngn1 had little or no effect on all lineages tested. Ultimately, the generation of a specific neuronal subtype may require a combination of different strategies, including genetic induction of neuronal commitment, as was performed here, and either addition of other transcription factors [35,40,61,65] or epigenetic manipulation of the cells [13,29,66].…”