Living science: Studying human brain tissue in a dish
March 23, 2015
At two in the morning, labs at the Allen Institute for Brain Science are quiet. Except for a few special nights when scientist Jonathan Ting and research associate Peter Chong are taking their 12-hour shifts, hovering over a piece of tissue about the diameter of a pea and not much thicker than a piece of paper. This tissue is so valuable for one crucial reason: It’s human.
“Working with living human brain tissue is very rare and very cool,” says Ting. “The hours are definitely long, but the results we’re getting are thrilling.”
Since early 2014, Ting has been collaborating with neurosurgeons at local Seattle hospitals to acquire small pieces of human brain tissue, the result of surgeries mostly on epilepsy patients. Time is of the essence with these precious pieces of brain because once they have been separated from their blood supply, they require bubbling oxygen from a portable gas tank to feed their metabolic needs. The brain pieces are very quickly transported back to the lab, where Ting and Chong trade shifts recording signals from individual cells in thin slices of tissue.
“There are only a handful of groups in the world using living human brain tissue from surgery for this kind of basic science research, and the scale at which we intend to do it is unlike anywhere else,” says Ting.
All 20 cases from which Ting and his team have received tissue in the last year have yielded valuable information. There have also been unexpected but welcome surprises, including the fact that many of those brain slices have lived for more than 48 hours in the dish.
“The human tissue has far exceeded anyone’s expectations in terms of how long it can live—nearly ten times longer than mouse brain slices,” explains Ting. “This has been extremely fortunate, since it means we can really take advantage of the tissue we are lucky enough to get.”
Each of the small slices of brain tissue is put in a recording chamber, where it is flooded with artificial cerebral spinal fluid and oxygen to help keep it healthy. Ting looks for landmarks that indicate plump, healthy cell bodies, and then uses a fine micromanipulator to gently push a tiny glass electrode against the cell membrane, which seals immediately around the pipette. He then uses the pipette, which is fitted with an even smaller electrode wire, to deliver bursts of electrical current to see how the cell reacts.
While Ting is taking these electrophysiological measurements, the pipette is also slowly filling the cell with a chemical called biocytin, which is later combined with a chemical reagent that darkens the fluid inside the cell so the cell’s elaborate shape can be captured in a light microscope.
“Getting this kind of data on human cells is so valuable, especially on tissue that would otherwise be considered ‘medical waste’ and discarded,” says Ting. “Scientists still don’t know how many types of cells are in our brains—or how to define a type of cell, for that matter—so getting to experiment directly on living human brain tissue is a very exciting way of moving toward our goal of understanding how the human brain works.”