Human motor neuron generation from embryonic stem cells and induced pluripotent stem cells

Abstract

Motor neuron diseases (MNDs) are a group of neurological disorders that selectively affect motor neurons. There are currently no cures or efficacious treatments for these diseases. In recent years, significant developments in stem cell research have been applied to MNDs, particularly regarding neuroprotection and cell replacement. However, a consistent source of motor neurons for cell replacement is required. Human embryonic stem cells (hESCs) could provide an inexhaustible supply of differentiated cell types, including motor neurons that could be used for MND therapies. Recently, it has been demonstrated that induced pluripotent stem (iPS) cells may serve as an alternative source of motor neurons, since they share ES characteristics, self-renewal, and the potential to differentiate into any somatic cell type. In this review, we discuss several reproducible methods by which hESCs or iPS cells are efficiently isolated and differentiated into functional motor neurons, and possible clinical applications.

Fig. 1

Differentiation of hSCs into motor neurons. Schematic procedures for the in vitro differentiation of hSC (a picture of iPS cells is shown here). hSC are differentiated into neural rosettes or neural precursors were produced by neural selection and expansion procedures after embryoid bodies formation. Neural precursors are differentiated into motor neurons by treating the cells with signaling molecules, such as Shh or Shh agonists, and RA. The cells achieved further maturation in the presence of motor neuron growth factors like BDNF or GDNF. In the lower picture, the detection of motor neurons from differentiated iPS was performed here by immunocytochemistry for SMI32, a neurofilament protein expressed by motor neurons