Study using living tissues provides new system to understand disease processes in amyotrophic lateral sclerosis and other disorders
A new study has revealed that the human brain's tiniest blood vessels can activate genes known to trigger spinal motor neurons, prompting the neurons to grow during early development. The findings could provide insights into how amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders may develop.
Layers of spinal motor neuron cells (top, in blue) and capillary cells (bottom, in red) converge inside an Organ-Chip. Neurons and capillary cells interact together along the length of the chip. The image was produced using a confocal microscope; colors were generated by staining with fluorescent antibodies.
Credit: Cedars-Sinai Board of Governors Regenerative Medicine Institute
To make the discovery, investigators successfully re-created living tissues of the blood vessels and the spinal motor neurons--which control muscles--outside the body to show how they interact.
"Until now, people thought these blood vessels just delivered nutrients and oxygen, removed waste and adjusted blood flow. We showed that beyond plumbing, they are genetically communicating with the neurons," said Samuel Sances, PhD, a postdoctoral fellow at the Cedars-Sinai Board of Governors Regenerative Medicine Institute. He is the first author of the study, published in the journal Stem Cell Reports.
When a human embryo is about four weeks old, Sances explained, new blood vessels begin to surround a primitive column of cells that eventually will become the spinal cord. Driven by developmental genes, some of these cells turn into spinal motor neurons. The study showed the cells of the brain's smallest blood vessels, known as capillaries, are capable of activating these genes, which can spur spinal motor neurons to grow and mature.
Besides providing insights into human biology, the study opened a new pathway to unraveling the mysteries of disorders such as ALS, or Lou Gehrig's disease, Sances said. ALS is a progressive, fatal disorder that kills motor neurons. There is no known cure. More than 6,000 people in the U.S. are diagnosed with the disorder each year, according to the ALS Association.
"What may go wrong in the spinal neurons that causes the motor neurons to die?" Sances asked. "If we can model an individual ALS patient's tissues, we may be able to answer that question and one day rescue ALS patients' neurons through new therapies."
The study's findings were made possible by a unique pairing of stem cell science with Organs-on-Chips technology, which re-creates human biology in micro-engineered environments.
Cedars-Sinai investigators first took samples of skin cells from adults and genetically reprogramed them into induced pluripotent stem cells, which can create any type of cell--in this case, spinal motor neurons and the lining of the brain's capillaries. The team placed these cells in the tiny channels of Organ-Chips, which are made of flexible polymer and are about the size of AA batteries. In the chips, nurtured by special fluids, the cells of the two different tissues thrived and interacted with each other.
"This study told us something important about how our neurons develop," said Clive Svendsen, PhD, professor of Medicine and Biomedical Sciences, director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute and senior author of the study. As a next step, he added, investigators are developing plans to use chip technology to compare the vessel-neuron interactions in ALS patients against those of individuals without ALS.
The research is part of the new Patient-on-a-Chip program, a collaboration between Cedars-Sinai and Emulate Inc. in Boston to help predict which disease treatments would be most effective based on a patient's genetic makeup and disease variant. Emulate produces the Organ-Chips used in the program. Geraldine A. Hamilton, PhD, Emulate's president and chief scientific officer, is a co-author of the spinal motor neuron study.
In February, investigators from the two organizations announced they had used an Intestine-Chip to model a human intestinal lining.
The Patient-on-a-Chip program is an important initiative of Cedars-Sinai Precision Health, whose goal is to drive the development of the newest technology and best research, coupled with the finest clinical practice, to rapidly enable a new era of personalized health.
Disclosure: Cedars-Sinai owns a minority stock interest in Emulate Inc. An officer of Cedars-Sinai also serves on Emulate's board of directors. Emulate provides no financial support for this research.
Funding: Research reported in this news release was supported by the National Institutes of Health Tissue Consortium 2.0 under award number 1UG3NS105703- 01, the ALS Association and the California Institute for Regenerative Medicine.
Video 1 caption:
3D video shows layers of spinal motor neuron cells (top, in blue) and capillary cells (bottom, in red) inside an Organ-Chip. Top-down view shows interconnected network of spinal motor neurons (blue) that interacts with the capillary cells below (in red). The video was produced using a confocal microscope; colors were generated by staining with fluorescent antibodies.
Video 1 credit: Cedars-Sinai Board of Governors Regenerative Medicine Institute
Video 2 caption:
Hundreds of spinal motor neurons spontaneously communicate through electrical signals inside an Organ-Chip. Neurons fire individually (flashing dots) and in synchronized bursts (bright waves). The activity was observed using a dye that fluoresces when neurons send an electrical signal.
Video 2 credit:
Cedars-Sinai Board of Governors Regenerative Medicine Institute
Jane Engle | EurekAlert!
Using fragment-based approaches to discover new antibiotics
21.06.2018 | SLAS (Society for Laboratory Automation and Screening)
Scientists learn more about how gene linked to autism affects brain
19.06.2018 | Cincinnati Children's Hospital Medical Center
In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.
Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...
Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...
Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.
Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...
The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.
Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.
An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.
Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...
13.06.2018 | Event News
08.06.2018 | Event News
05.06.2018 | Event News
22.06.2018 | Materials Sciences
22.06.2018 | Earth Sciences
22.06.2018 | Life Sciences