Many existing methods seed heart cells or stem cells on a momentary “scaffold”: a porous, spongy substance that can hold them in location within 3 dimensions.” If you have scaffold thats just a few cells thick, you can get cells into the best place. Even if youre doing 1,000 cells per 2nd, you still have to lay down lots of billions of cells to get an organ. Once theyre printed, the researchers need to in some way encourage them to differentiate into more particular cell types, forming a multilayered cluster of working cell groups that resemble healthy organ tissue. Some cells are programmed to end up being cardiomyocytes, the heart cells that form the core practical tissue within the heart.
Using sophisticated 3D printing strategies, Mark Skylar-Scott and his group of Stanford bioengineers want to transform a paste made of living cells into hearts and other organs.
For an engineer, couple of human organs are more attracting than the human heart. As an outcome, thousands of young patients with innate heart conditions need to cope with their disease for a life time.
” Pediatric heart problem is one of the most typical types of hereditary birth defects in the U.S.,” says Mark Skylar-Scott, assistant professor of bioengineering in the schools of Engineering and Medicine. “Its really tough on households. There are ways to extend lives of children with surgery, however lots of kids struggle with constraints on activity and live a life filled with uncertainty. To have a genuinely alleviative option, youll require to in some way replace malformed or damaged tissue.”
Stanford researchers work to produce human tissues at healing scale, with a focus on the heart. Credit: Kurt Hickman
Thats where Skylar-Scott comes in. Hes dealing with brand-new ways to approach congenital heart disease by developing engineered heart tissue in the laboratory.
It takes even more than just culturing cells in a dish, he keeps in mind. A lot of existing techniques seed heart cells or stem cells on a temporary “scaffold”: a porous, spongy compound that can hold them in place within 3 measurements. That approach lets scientists grow lab-made tissue, its only actually practical for incredibly thin layers of cells.
” If you have scaffold thats just a few cells thick, you can get cells into the right location. However if you try to grow something thats a centimeter thick, it gets truly tough to seed cells within the right areas to grow tissue. It ends up being a real obstacle to keep them alive, get them the ideal nutrients or get vasculature to them,” Skylar-Scott states. Human organs are also not monolithic balls of cells, he includes. Each one is made from an intricate layers of multiple cell types, resulting in 3D structure thats extremely tough to reproduce.
Printing organoids
To navigate this reality, Skylar-Scott and his team are dealing with a strong brand-new angle for growing organs. Using innovative 3D printing methods, theyre making thick tissues one layer at a time, putting the exact kind of cells required at the ideal areas like a tower rising from a grid of thoroughly put bricks. This sort of building approach, he notes, works well for duplicating intricate tissues like the heart, where 3D form matters significantly for its function.
As appealing as it might be, 3D printing with cells features some thorny and deep obstacles. Unlike plastic filament, which consumer 3D printers can heat up and squeeze into myriad shapes, cells live. Theyre soft, squishy, imperfect, and frustratingly fragile, says Skylar-Scott.
The 3D bioprinter prints a sample. Credit: Andrew Brodhead
” If you attempt to position a single cell at a time, printing a liver or heart might take hundreds or thousands of years. Even if youre doing 1,000 cells per second, you still have to put down many billions of cells to get an organ. If you do the mathematics, that does not turn out too perfectly for a scalable procedure,” he states.
Instead, Skylar-Scott and his lab are working to accelerate the printing process by putting down dense clumps of cells called “organoids.” The group creates these clumps by putting genetically modified stem cells in a centrifuge, which creates a pastelike compound. Using this concoction, theyre able to print a great deal of cells simultaneously into a gelatinous 3D structure. “We basically define the massive structure of an organ by printing these organoids,” he says.
Cell programs
Getting the stem cells in place is just the initial step, however. Once theyre printed, the scientists should in some way persuade them to separate into more particular cell types, forming a multilayered cluster of working cell groups that look like healthy organ tissue. To achieve this, Skylar-Scott basically bathes the stem cells in a chemical cocktail.
” Each line of stem cells we are establishing are genetically crafted to respond to a particular drug,” he notes. “Once they pick up that drug, they distinguish into specific cell types.” Some cells are set to end up being cardiomyocytes, the heart cells that form the core practical tissue within the heart. Others are instructed to become stromal cells, which bond the tissues together.
Skylar-Scott is checking his printed tissues in a bioreactor, a container about the size of a smartphone that helps to keep the printed cells alive. Inside it, his group had the ability to grow a printed organ-like structure: a tube approximately 2 inches long, and half a centimeter in diameter. Like a vein inside the human body, this tiny gadget could “pump” by itself, contracting and broadening to move fluid through itself.
” If we can establish more tissues like this, we may have a good halfway point to developing something that can be implanted in the human body,” says Skylar-Scott. “For clients born with a single ventricle, for instance, theres just one chamber in the heart that can press blood through into the body and the lungs– which puts a lot of pressure on the cardiovascular system and triggers hypertension that can produce organ damage. Something like this could function as a biological pumping gadget to help blood get to and from the heart,” he states.
Scale-up
Skylar-Scott fasts to keep in mind that printing a larger structure, like a functional chamber to graft onto an existing heart, is still a methods off. Producing that would suggest growing something more than 16 times the size of his labs experimental “vein pump.” In order to produce something even near that size– or even better, a whole new organ– his laboratory would require to scale up cell production enormously.
” Scale-up is going to be the obstacle of our generation,” states Skylar-Scott. Itll mean more just developing a larger printer, nevertheless. In numerous methods, it boils down to the cells themselves.
” Right now, it takes a month to grow adequate cells to print something tiny. Its extremely costly to do also– each test represents 10s of thousands of dollars,” he states. “We need to find out ways to engineer cells to make them more robust and cheaper to grow, so we can start practicing and perfecting this approach. Once the pipeline for new cells remains in location, I believe were going to start seeing some incredible progress.”