Electrically Active Motor Neurons Made from iPS Cells

Discovery demonstrates the feasibility of using iPS-derived motor neurons to model and treat diseases Wednesday, 25 February 2009 Stem cells scientists at UCLA showed for the first time that human induced pluripotent stem (iPS) cells can be differentiated into electrically active motor neurons, a discovery that may aid in studying and treating neurological disorders. Additionally, the motor neurons derived from the iPS cells appeared to be similar in function and efficiency to those derived from human embryonic stem cells, although further testing needs to be done to confirm that. If the similarities are confirmed, the discovery may open the door for new treatments for neurological disorders using patient-specific cells. "It is clear from the literature that you can make at least immature versions of many different kinds of cells from human iPS cells," said William Lowry, a Broad Stem Cell Research Center scientist, an assistant professor of molecular, cell and developmental biology and senior author of the study. "But there is not a lot of data published describing the generation of fully functional cells from human iPS cells." 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 signalling. 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 modelling 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." "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. "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. "It seems possible that disease-specific somatic cells may be reprogrammed and utilized to model, and ultimately to treat a variety of human neurological disorders," says Miodrag Stojković, co-editor of the journal. 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. Reference: Directed differentiation of human induced pluripotent stem cells generates active motor neurons (p N/A) S Karumbayaram, BG Novitch, M Patterson, JA Umbach, L Richter, A Lindgren, AE Conway, AT Clark, SA Goldman, K Plath, M Wiedau-Pazos, HI Kornblum, WE Lowry Stem Cells, Online: Feb 23 2009, DOI: 10.1002/stem.31 ......... ZenMaster

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