Scientists reported Sunday that they coaxed human embryonic stem cells to become spinal motor neurons, critical nervous system pathways that relay messages from the brain to the rest of the body.
The new research, published in the on-line version of the journal Nature Biotechnology, was conducted by Chinese scientists working at the University of Wisconsin-Madison.
Motor neurons can transmit messages from the brain and spinal cord, dictating almost every movement in the body from the wiggling of a toe to the rolling of an eyeball.
The development is important because it provides critical guideposts for scientists trying to repair damaged or diseased nervous systems, said research leader Su-chun Zhang.
One day it may help victims of spinal-cord injuries, or pave the way for novel treatments of degenerative diseases such as amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, Zhang said.
Scientists have long believed in the therapeutic promise of embryonic stem cells with their ability to replicate indefinitely and develop into any of the 220 different types of cells and tissues in the body, but they have failed to convert embryonic stem cells into motor neurons.
The goal proved elusive even in mice, whose embryonic stem cells have been available to scientists for decades.
One reason may be that they are one of the earliest neural structures to emerge in a developing embryo, Zhang and colleagues said.
With the ticking clock of development in mind, Zhang and his team deduced that there is only a thin sliver of time, roughly the third and fourth week of human development, in which stem cells could be successfully prodded to transform themselves into spinal motor neurons.
In addition to the narrow time frame, it was also critical to expose the growing stem cells to an array of complex chemical cocktail. The cocktail is constituted by a mix of growth factors and hormones that provide the exact growing conditions needed to steer the cells down the correct developmental pathway.
"You need to teach the embryonic stem cells to change step by step, and each step has different conditions and a strict window of time," Zhang said.
To differentiate into a functional spinal motor neuron, the stem cells advanced through a series of mini-stages, each requiring a unique growing medium and precise timing. To start, the Wisconsin team generated neural stem cells from the embryonic stem cells. They then transformed the neural cells into progenitor cells of motor neurons, which in turn developed in a lab dish into spinal motor neuron cells.
The newly generated motor neurons exhibit telltale electrical activity, a sign that the neurons were functional, Zhang said.
The discovery demonstrates that human stem cells do not necessarily differentiate in linear fashion, as scientists always believed. Rather, a series of complex overlapping changes may well be the developmental norm in higher vertebrates such as humans.
"This research proved a basic principle of growing human embryonic stem cell-- you must give the cells specific stimulations at specific time," Zhang told Xinhua.
(Xinhua News Agency February 1, 2005)
