Directed Differentiation of Embryonic Stem Cells into Motor Neurons

Abstract

Inductive signals and transcription factors involved in motor neuron generation have been identified, raising the question of whether these developmental insights can be used to direct stem cells to a motor neuron fate. We show that developmentally relevant signaling factors can induce mouse embryonic stem (ES) cells to differentiate into spinal progenitor cells, and subsequently into motor neurons, through a pathway recapitulating that used in vivo. ES cell-derived motor neurons can populate the embryonic spinal cord, extend axons, and form synapses with target muscles. Thus, inductive signals involved in normal pathways of neurogenesis can direct ES cells to form specific classes of CNS neurons.

Engineering personalized neural tissue by combining induced pluripotent stem cells with fibrin scaffolds

“…The application of both RA and Shh during embryoid body formation in murine ESCs was investigated by Wichterle et al [22], Miles et al [23], Kothapalli and Kamm [24], Brown et al [25], and in human ESCs by Li et al [26], Stacpoole et al [27], and Hu and Zhang [28], among others. Such studies have revealed the synergistic effects of these two factors.…”

Electrophysiological evaluation of engrafted stem cell-derived neurons

“…These neurons can be tailored, in cell culture, to display striking morphological and immunophenotypic similarities to cells found in the adult brain, and even to cells lost during the course of brain disease [1][2][3][4][5][6][7][8][9][10] . Because stem cell-derived neurons are born in a culture dish, without the environmental cues of the developing brain, it has become a major quest to determine whether these cells are actually functional, that is, capable of interacting with established neural circuitry.…”

Recent Advances and the Future of Stem Cell Therapies in Amyotrophic Lateral Sclerosis

“…Given that the goal of early stem cell therapies for ALS were directed at MN replacement, the finding that MNs derived from mouse embryonic stem cells could be grafted into a chick spinal cord and synapse with muscles was exciting [95]; however, results of similar studies in rodent models of ALS were not met with the same success, likely related to features of both ALS, as well as the challenges of reconstructing the motor system as mentioned above. For example, SOD1-G93A rats that underwent grafting of mouse embryonic stem cells into the spinal cord only exhibited a transient motor improvement that may have been due to trophic support provided by the grafted MNs to the degenerating endogenous MNs [11].…”