The shortage of transplantable organs has spawned a fascinating science and market. A liver, for example, is often split among two recipients, while for a cystic fibrosis patient in need of two lungs, it is technically preferable to just swap out both the heart and lungs as a combo unit. The extra heart can then be domino donatedto a third party. Bioprinting complete organs en masse is a tough proposition because the identity expressed by each component cell must be individually programmed. Then the cells need to be knitted together in a developmentally sound fashion. Researchers in Scotland, land of Dolly, the first cloned mammal, have recently demonstrated the ability to print human embryonic stem cells. Stem cells, of course, are known for a unique feature — they can program themselves.
It was announced at the end of last year, that Autodesk, the makers of CAD software like AutoCAD, would be partnering with a new startup by the name of Organovo to make 3D organ printing a reality. While it is encouraging to see engineering tools rigorously applied to the life sciences, it should be recognized that printing something that looks like an organ does not mean it will actually be an organ. In the short term at least, the main goal of the startup is to produce some tissues which may be able to serve as a testbed for pharmaceuticals. The new stem cell study, published this week in the journal Biofabrication, looks to create tissues pregnant with real organ-producing power, and may prove to be just what the doctor ordered.
So, in 20 years, will replacement organs be printed, grown, or built?
While stem cells from a mouse have been printed before, human stem cells have proven to be a bit more fragile and generally more difficult to work with. Part of the problem is due to subtle differences in the required cellular nutrient environments (think about some dogs getting pancreatitis from eating bacon), and part is also due to the fact that researchers are simply more familiar with the mouse cells. For the specific needs of the Scotland researchers, commercial 3D printers were far too crude, so they built their own by modifying a precision CNC machine that was capable of micron step resolution. Using dual extrusion heads to deliver cells and media, they could deposit cells with just right amount of personal space to make them feel at home and comfortable.
By fine manipulation of the dispensing aperture, extrusion pressure, and viscosity of the bioink, the researchers could print spheroids of cells that varied between five and 140 cells. When a bank of spheroids was complete, they were inverted and the cells could coalesce at the bottom under the influence of gravity. One new technique that would be of great benefit here would be to feed the cells a few ferrite beads and position them instead with maglev manipulation.
Before getting too carried away, there are many important checks that need to be run to make sure the stem cells retain pluripotence after having been traumatically birthed through the extruder. In other words, they may still be alive, but if they have lost the ability to turn into any kind of cell, organs are not going to happen. The researchers did a partial check on this, finding that the cells continued to manufacture a particular control protein that helps keep them in a youthful state. The real test will be how the cells respond when they must compete for oxygen and fuel in a proto-organ matrix that more closely mimics conditions in the body.
All too often with cancers, several organs have been infiltrated by tumors but the organs themselves are still functional. When the cancer doesn’t respond to drugs anymore, and traditional surgery is impossible because the critical vasculature has become so gnarled with disease and previous radiation treatments, the patient has typically reached the end of the line. The inevitable merging of 3D print systems with surgical robots will enable in siturepairs that surgeons would never even dream about doing by hand in the span of a single shift, extending the life of these patients. At the extreme, we can imagine an ingenious solution to the cell identity programming problem — the organ is printed inside the patient from a real prototype that is first deconstructed by enzyme, then reconstituted cell-by-cell with the proper local and connections. This is the technology of the future that so many in hospitals wait for today.