12 August 2002. In theory, embryonic stem (ES) cells have the inherent potential to differentiate into any cell in the body. In practice, making them grow into specific cell types has proven extremely difficult. In today’s issue of the journal Cell, researchers at Columbia University, New York, report they have figured out a way to coax ES cells into becoming motor neurons, opening up some exciting new possibilities for treating a variety of diseases, such as amyotrophic lateral sclerosis (ALS), caused by motor neuron damage.
First author Hynek Wichterle, working with Columbia’s Thomas Jessell and colleagues at Curis, Inc. in Cambridge, Massachusetts, capitalized on some groundbreaking research from their own and other labs, which elucidated the metabolic pathways that need to be activated for precursor cells to develop into motor neurons (see, for example, Briscoe and Ericson for a review). They turned these pathways on in ES cells using a variety of signaling molecules, including retinoic acid and the proteins hedgehog and sonic hedgehog, and then determined the fate of the cells by examining their morphology and expression of essential motor neuron proteins, or markers, such as the homeodomain protein, HB9.
The technique was so successful that they were able to take the partially differentiated cells and insert them into chicken embryos. The cells populated the chick spinal cords producing long axons that formed synapses with muscles, a prerequisite for functioning motor neurons.
The next step will be to prove that these neurons are active and can translate neuronal impulses into action. It also remains to be seen whether the differentiated cells will make any synaptic connections when introduced into adult animals, which may lack essential signaling molecules that would be found in developing embryos. -Tom Fagan
Reference:Wichterle H, Lieberam I, Porter JA, Jessel TM. Direct differentiation of embryonic stem cells into motor neurons. Cell 2002 August 9;110:385-397. Abstract