- December 05, 2019
The disease models comprise microglia — the immune cells of the brain — as well as neurons. They are the work of a collaboration between researchers at Aspen Neuroscience in La Jolla, California, the New York Stem Cell Foundation Research Institute and San Diego-based Summit for Stem Cell. The team created them from blood or skin cells taken from Parkinson’s and MS patients, said Aspen’s R&D Head Andres Bratt-Leal, Ph.D., during a teleconference early in July.
The researchers programmed those cells into induced pluripotent stem cells and then nudged them to become the types of neurons affected by Parkinson’s and MS — dopaminergic neurons and cortical neurons, respectively, Bratt-Leal told FierceBiotech. The researchers hope to learn how the microglia and neurons change and interact with each other in the absence of gravity — something they can not do on Earth. “One reason we are excited about microgravity is we are hearing more and more about astronauts’ immune systems being affected by microgravity,” Bratt-Leal said. “We know immune cells in the blood change shape in order to become activated. It’s very probable that forces on the cell affect how that cell responds and changes shape. When we remove those forces, it changes those cells’ ability to begin that process.” The models could point to a new way to treat Parkinson’s or MS based on controlling how cells respond to forces that could affect their activation, he said. However, they will need more experiments and more launches before they get there.
The National Stem Cell Foundation describes this launch as a preliminary flight in preparation for a first-of-its-kind study of neurodegeneration in microgravity scheduled for the ISS later this fall.
Once aboard, these first models will spend one month in a fully automated bioreactor created by Space Tango — so the astronauts won’t need to babysit them, Valentina Fossati, Ph.D., a Senior Research Investigator at the New York Stem Cell Foundation Research Institute, told FierceBiotech. At the end of their sojourn, the cells will be “fixed” so that anything that happened to them in space will not be affected by their return journey.
Back on Earth, Fossati’s team will carry out microscopic analyses to see how the cells changed, while Bratt-Leal’s lab will carry out whole-genome RNA sequencing. “We want to figure out all the genes in the genome that are being expressed. Are certain pathways upregulated or downregulated? We will also design follow-up experiments to modulate those pathways,” Bratt-Leal said.
Unlike an earlier shipment of tissue chips — tiny 3D models of human organs — that launched to the space station in May, the Parkinson’s and MS models are not considered “minibrains.” That is because they contain only certain types of neurons and microglia. “With ‘minibrains,’ we’re talking about lots of different types of neurons that have some structure or order to them. That’s not what we’re looking at,” Bratt-Leal said. However, they do share a similar purpose: to model diseases and test drugs in areas where animal models are lacking. “The problem with mouse models for the diseases we are studying, progressive multiple sclerosis and Parkinson’s disease, is that there are no good mouse models,” Fossati said.
Scientists have tried to get around this by using microglia from cadaver brains; however, those are hard to come by, she said. In 2016, Fossati’s team was among the first to figure out how to make microglia from stem cells.
The models were departed from Cape Canaveral, Florida, on July 21 as part of more than 5,500 pounds of science, cargo and crew supplies for the space station’s microgravity lab. The launch was postponed to July 24 at 6:24 p.m. EDT.
REFERENCE: Fierce BioTech; 22 JUL 2019; Amirah Al Idrus