Last week, researchers from Cedars-Sinai Medical Center added a new piece to the complex puzzle of what causes neurodegenerative disorders like amyotrophic lateral sclerosis (ALS). The team discovered that the tiny blood vessels in our brains do more than provide nutrients to and remove waste products from our brain tissue. It turns out that these blood vessels can stimulate the growth of new nerve cells called spinal motor neurons, which directly connect to the muscles in our body and control how they move. The study, which was funded in part by a CIRM Discovery research-stage Inception award, was published in the journal Stem Cell Reports.

The Cedars team used a combination of human induced pluripotent stem cells (iPSCs) and organ-on-a-chip technology to model the cellular microenvironment of the spinal cord. They matured the iPSCs into both spinal motor progenitor cells and brain endothelial cells (which line the insides of blood vessels). These cells were transferred to an organ-chip where they were able to make direct contact and interact with each other.

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. (Cedars-Sinai Board of Governors Regenerative Medicine Institute).

The researchers discovered that exposing the spinal motor progenitor cells to the blood vessel endothelial cells in these organ-chips activated the expression of genes that directed these progenitor cells to mature into spinal cord motor neurons.

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). (Cedars-Sinai)

First author on the study, Samuel Sances, explained their findings in a news release:

“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.”

The team also showed the power of stem cell-based organ-chip platforms for modeling diseases like ALS and answering key questions about why these diseases occur.

“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.”

Clive Svendsen, a CIRM grantee and the senior author on the study, said that his team will conduct additional studies using organ-chip technology to study the interactions between iPSC-derived neurons and blood vessels of healthy individuals and ALS patients. Differences in these cellular interactions in diseased patient cells could offer new targets for developing ALS therapies.

The current study is a collaboration between Cedars and a Boston company called Emulate, Inc. Emulate developed the organ-chip technology and is collaborating with Svendsen at Cedars to not only model neurodegenerative diseases, but also model other organ systems. Be sure to check out our recent blog about their efforts to create a stem cell-based gut-on-a-chip, which they hope will pave the way for personalized treatments for patients with gastrointestinal diseases like Chrohn’s and inflammatory bowel disease.