Neural stem and progenitor cells in health and disease

Abstract

Neural stem/progenitor cells (NSPCs) have the potential to differentiate into neurons, astrocytes, and/or oligodendrocytes. Because these cells can be expanded in culture, they represent a vast source of neural cells. With the recent discovery that patient fibroblasts can be reprogrammed directly into induced NSPCs, the regulation of NSPC fate and function, in the context of cell-based disease models and patient-specific cell-replacement therapies, warrants review.

Figure 1

Successful cell transplantation of human ESC-derived dopaminergic neurons into a monkey model of PD (MPTP lesioned rhesus monkeys). Left, representative graft 1 month after transplantation, showing expression of the dopaminergic neuron marker Tyrosine Hydroxylase (TH), with surrounding TH+ fibers (arrows). Right, co-expression of human specific cytoplasm marker SC-121 (red) and TH (green) in graft.

Figure 2

Paradigm of a high-throughput screen for small-molecules capable of neural protection of ESC-derived motor neurons and astrocytes in the presence of activated microglia. After screening more than 10,000 small molecules, the 0.3% hit rate included compounds acting in the activation of the Nrf2 pathway in microglia and astrocytes, direct protection of neurons from nitric-oxide-induced degeneration and inhibition of nitric oxide production by microglia. (Adapted from Hoing et al, 2011)