Directed Differentiation of Human-Induced Pluripotent Stem Cells Generates Active Motor Neurons

Abstract

The potential for directed differentiation of human-induced pluripotent stem (iPS) cells to functional postmitotic neuronal phenotypes is unknown. Following methods shown to be effective at generating motor neurons from human embryonic stem cells (hESCs), we found that once specified to a neural lineage, human iPS cells could be differentiated to form motor neurons with a similar efficiency as hESCs. Human iPS-derived cells appeared to follow a normal developmental progression associated with motor neuron formation and possessed prototypical electrophysiological properties. This is the first demonstration that human iPSderived cells are able to generate electrically active motor neurons. These findings demonstrate the feasibility of using iPS-derived motor neuron progenitors and motor neurons in regenerative medicine applications and in vitro modeling of motor neuron diseases.

Concise Review: Induced Pluripotent Stem Cells Versus Embryonic Stem Cells: Close Enough or Yet Too Far Apart?

“…Categorizing the genes in iPSC affected by mutations brings forward, if any, genes implicated in the cell cycle regulation and tumors [46,70]. Although the spread of the mutations in the genome of iPSC is pretty wide, there are some more frequent mutations and chromosomal aberrations that are common to late passage human ESC, too.…”

Cell Therapy for Multiple Sclerosis

“…Although the use of ES cells dictates an allogeneic donor cell source, the recent generation of induced pluripotential stem (iPS) cells from somatic mouse [213] cells and from human [214,215] [216][217][218] and oligodendrocytes [219,220]. It will now be necessary to explore the potential for generating populations of iPS-derived oligodendrocytes for autologous grafting in the myelin disorders.…”

Concise Review: Stem Cells for the Treatment of Cerebellar-Related Disorders

“…Although iPS cells-derived neural subtypes have not yet been applied on any experimental model of cerebellar ataxia, a number of research groups have been evaluating neural differentiation potential and function of human iPS cells in neurodegenerative disease animal models [43,44]. In our hands, results indicate that iPS cells can be differentiated toward cerebellar-like cells using the same differentiation strategy as the one applied to hESC (Erceg et al, unpublished results).…”