New organ-on-chip technology modeling human spinal cords could one day lead to personalized treatments for neurological disorders.
A team of researchers, funded by the National Institutes of Health (NIH), reprogrammed stem cells originally derived from human skin into induced pluripotent stem (iPS) cells, in order to recreate interactions between blood vessels and neurons that may occur early in the formation of the fetal human spinal cord. iPS cells can also be used to study diseases for which there are no adequate human in vitro or animal models.
Danilo Tagle, PhD, MS, associate director for special initiatives of the NIH’s National Center for Advancing Translational Sciences, explained how the technology could lead to new therapeutics for neurological diseases like ALS and Parkinson’s disease.
“Essentially, the main premise behind organs-on-chips or tissues-on-chips is to come up with an in vitro device or tool that can be used to assess the safety and efficacy of therapeutics, whether it be a small molecule or a biologic or a micromolecule,” Tagle said, in an interview with R&D Magazine. “The ability to generate various organ systems—in this particular case the spinal cord and blood brain barrier—would enable the ability to screen for drugs that could essentially cross the blood brain barrier.”
According to Tagle, many drugs are unable to cross the blood brain barrier, making neurological diseases unamenable to many new therapeutic approaches. However, the new technology could enable researchers to quickly discover whether new drug candidates can cross the blood-brain barrier.
In the study, the researchers first converted the stem cells into newborn spinal cord neurons, or endothelial cells, which line the walls of brain blood vessels. For most experiments, each cell type was injected into one of two chambers embedded side-by-side in thumb-sized, plastic tissue chips and allowed to grow.
After six days, the team found that the growing neurons exclusively filled their chambers, while the growing blood vessel cells lined their chamber in a cobblestone pattern similar to vessels in the body.
The growing blood vessel cells also snuck through the perforations in the chamber walls and contacted the neurons, which enhanced maturation of both cell types and caused the neurons to fire more often.
“The results show that the vascular system has specific maturation effects on spinal cord neural tissue, and the use of Organ-Chips can move stem cell models closer to an in vivo condition,” the study states.
Tissue chips—which are a relatively new tool for medical researchers—help researchers grow cells in more life-like environments. The researchers built the chambers using microprocessor-manufacturing techniques to recreate the 3D shapes of critical organ parts and the tight spaces that mimic the way viscous, bodily fluids normally flow around cells.
Using tissue chips allows researchers to grow neurons and blood vessels together, which was impossible to do using the traditional petri dishes. In addition, neurons grown alone in tissue chips had firing patterns and gene activity that was more mature than the cells grown in petri dishes.
Tagle explained how the researchers could implement the new technology in a pre-clinical setting.
“The next step would be to take stem cells from patients and reconstruct them into the same system, making organ-on-chip disease models,” he said. “You are able to then test for candidate drugs in the system and once those drugs are tested and shown to be effective, that’s where it will impact the clinical setting so you can use those drugs to actually do your clinical trials.”
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.
The study was published in Stem Cell Reports.