Simulating the Gut-Brain Axis using iPSC and Organ-Chip Technology: A New Model of Parkinson's Disease
There are hints that the gut and its beneficial bacteria – the gut microbiome – directly and negatively affect the brain in people with Parkinson’s disease, a devastating neurological disease that affects millions of people around the world, but the details of these interactions remain unclear. Clive Svendsen has led the development of methods to study human stem cells and stem cell-derived mature cells in “organ-on-chip” technologies, simulating aspects of human organs in the lab. Now, Svendsen is leading a team to investigate the complex interplay between gut cells, neurons and the microbiome in patients with Parkinson’s disease, using these methods to model the gut-brain axis in the lab, pairing a gut-chip laced with human microbiome and a brain-chip to explore how the gut cells and microbes might hasten neuron death. His findings could lead to new insights into the disease, provide a new avenue to test therapies and, more broadly, shed light on the mysterious ways our microbiome influences our brains.
Clive Svendsen, Ph.D.
Clive Svendsen is a professor of medicine and biomedical sciences and director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute. The institute's 130 scientists, including 20 faculty, perform research that aims to model and treat diseases using stem cells and regenerative medicine approaches, including gene therapy. Key programs involve blood, brain, eye, gut, lung, liver and kidney, and skeletal tissues.
One focus of Dr. Svendsen's research is to derive cells from patients with specific disorders that can then be "reprogrammed" to a primitive state and used as powerful models of human disease. These cells are known as induced pluripotent stem cells, or iPSCs. Svendsen led the first groups to successfully model spinal muscular atrophy and, more recently, Huntington's disease using this technology. He is co-director of the global Answer ALS Research Program, which is building a comprehensive clinical, genetic, molecular and biochemical assessment using iPSC cells derived from 1,000 patients with amyotrophic lateral sclerosis (ALS).
The other focus of Dr. Svendsen's research involves cutting-edge clinical trials. He is currently working with neurosurgeons, neurologists and other scientists to develop novel ways of using stem cells, modified to release growth factors, to treat patients with neurological disorders, including ALS and Huntington's, Alzheimer's and Parkinson's diseases. He recently completed a clinical trial to test a combination stem cell-gene therapy developed at Cedars-Sinai to stall the progression of ALS and has received FDA approval to conduct a similar trial involving retinitis pigmentosa.
Dr. Svendsen is the Kerry and Simone Vickar Family Foundation Distinguished Chair in Regenerative Medicine at Cedars-Sinai. Among other recognitions, he has received the Sheila Essey Award for ALS Research from the American Academy of Neurology (2010); the Commitment to a Cure Award from the ALS Association (2010); and the Huntington's Disease Society of America Trailblazer Award (2009). His laboratory's innovative stem-cell work was featured on the cover of National Geographic in January 2019.