Feb. 25, 2009 In a new study, researchers were able to generate functionally mature motor neurons from induced pluripotent stem (iPS) cells, which are engineered from adult somatic cells and can differentiate into most other cell types.
A potential new source of motor neurons that does not require human eggs or embryos could be an enormous boon to research into conditions such as amyotrophic lateral sclerosis (ALS) and spinal cord injury and could open the door to eventual treatments.
This study is the first to use human iPS cells to generate electrically active motor neurons, a key hallmark of functional maturation that is essential for any future application of iPS cells. “To our knowledge, our results present the first demonstration of the electrical activity of iPS-derived neurons and further suggest the feasibility of using these cells to explore how changes in motor neuron activity contributes to the degeneration of these cells underlying these disorders,” the authors state.
Led by William Lowry, and in collaboration with Bennett Novitch, Harley Kornblum, and Martina Wiedau-Pazos of the University of California Los Angeles, researchers compared the ability of different human cell lines to generate motor neuron progenitors and fully differentiated motor neurons. “These findings support the possibility that reprogrammed somatic cells might prove to be a viable alternative to embryo-derived cells in regenerative medicine,” the authors note.
When measuring the electrophysical properties of the iPS-derived neurons, the researchers found that the iPS cells followed a normal developmental progression to mature, electrically active neurons.
Lowry and his team used skin fibroblasts and reprogrammed them back into an embryonic state, with the ability to differentiate into any cell type in the human body. They then took those cells and differentiated them into motor neurons.
Neurons are the responsive cells in the nervous system that process and transmit information by electrochemical signaling. Motor neurons receive signals from the brain and spinal cord and regulate muscle contraction.
The study demonstrates the feasibility of using iPS-derived motor neurons and their progenitors to replace damaged or dead motor neurons in patients with certain disorders. It also opens the possibility of studying motor neuron-related diseases in the laboratory to uncover their causes. Motor neurons are lost in many conditions, including spinal cord injury, Amyotrophic Lateral Sclerosis and Spinal Muscular Atrophy.
"A primary objective of human embryonic stem cell and human iPS cell technology is to be able to generate relevant cell types to enable the repair of tissue damage and in vitro modeling of human disease processes," the study states. "Here, we demonstrate the successful generation of electrically active motor neurons from multiple human iPS cell lines and provide evidence that these neurons are molecularly and physiologically indistinguishable from motor neurons derived from human embryonic stem cells."
Much may be learned from studying the iPS-derived motor neurons and comparing them to motor neurons derived from patients with neurological disorders to see how they differ. The next step for Lowry and his team is to combine the motor neurons with muscle cells to see if they can stimulate a response. If they do, researchers should be able to see the muscle cells contract.
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- Karumbayaram et al. Directed differentiation of human induced pluripotent stem cells generates active motor neurons. Stem Cells, 2009; N/A DOI: 10.1002/stem.31
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