Here I'll point to a recent selection of news and research relating to tissue engineering and organ regeneration. If you look around at the state of this field, organoids and proto-organs and pseudo-organs are everywhere. Many laboratories are making strides in the generation of small sections of functional or partly functional complex organ tissue. Alongside and overlapping this work is the young field of bioprinting, the use of 3-D printers to create tissue from scratch, layer by layer, depositing scaffold biomaterials, protein solutions, and cells in precise locations and amounts to form complex structures that themselves self-assemble in further growth. Further, there is the parallel approach of regenerating and rebuilding existing organs in situ, built on the same underlying knowledge, but aiming to deliver cells and protein signals to spur regrowth inside the body that would otherwise not happen.
These lines of work are entwined with one another, linked together in often novel ways. For example, much of the present focus in organ engineering is not in fact to produce complete and fully functional tissues for transplantation, as that still lies a way in the future for most complex organs, but rather to create tools to speed up life science research. Organoids and proto-organs, even if only partly functional, are a much better and cheaper option than animal models when it comes to studying both diseased and healthy tissues. Anything that lowers the cost and increases the quality of the tools needed for research will speed up progress. So the researchers aiming to understand the molecular biology of regeneration sufficiently well to steer it in the body will in years ahead be working with tissue engineering organoids for their early stage research and initial technology demonstrations.
I don't think it overly ambitious at this point to expect the late 2020s to be a time of comprehensive organ engineering, with the production of most tissues - to order, as needed - being a widely available option in clinical practice. It will be interesting to see the degree to which transplantation flourishes in the face of the growing ability to instruct cells in the body to repair existing organs. After all, removing the need for potentially traumatic, expensive, and risky major surgery is a big incentive to improve stem cell therapies and regenerative medicine to their theoretical limits rather than focus on building new patient-matched organs for transplant.
"We've been able to take MRI images of coronary arteries and 3-D images of embryonic hearts and 3-D bioprint them with unprecedented resolution and quality out of very soft materials like collagens, alginates and fibrins. 3-D printing of various materials has been a common trend in tissue engineering in the last decade, but until now, no one had developed a method for assembling common tissue engineering gels like collagen or fibrin. The challenge with soft materials - think about something like Jello that we eat - is that they collapse under their own weight when 3-D printed in air. So we developed a method of printing these soft materials inside a support bath material. Essentially, we print one gel inside of another gel, which allows us to accurately position the soft material as it's being printed, layer-by-layer." One of the major advances of this technique, termed FRESH, or "Freeform Reversible Embedding of Suspended Hydrogels," is that the support gel can be easily melted away and removed by heating to body temperature, which does not damage the delicate biological molecules or living cells that were bioprinted.
Starting with stem cells from the small intestines of human infants and mice, Hackam and his colleagues have for the first time grown intestinal linings on gut-shaped scaffolds that could one day treat bowel disorders like necrotizing enterocolitis and Crohn's disease. They have found that the tissue and scaffolding are not rejected, but instead readily assimilate in lab animals. Most strikingly, the scaffold allowed dogs to heal from damage to the colon lining, restoring healthy bowel function. The scaffold is made from a material similar to surgical sutures that can be formed into any desired intestinal size and shape, and is tube-shaped like a real gut, with tiny projections on the inner surface to help the tissue grow into functional small intestine villi, tiny fingers of tissue that help absorb nutrients. To grow the gut lining in the lab, the researchers painted the scaffold with a sticky substance containing collagen, dribbled it with a solution of small intestine stem cells, and then let it incubate for a week. They found that adding connective tissue cells, immune cells, and probiotics - bacteria that help maintain a healthy gut - helped stem cells mature and differentiate.
"With this paper, we've identified the signaling pathways in thyroid cells that regulate their differentiation, the process by which unspecialized stem cells give rise to specialized cells during early fetal development." After deciphering this natural differentiation process, the investigators duplicated it in the laboratory dish by adding a sequence of proteins, called growth factors, to the fluid bathing the stem cells. The team then used murine pluripotent stem cells to regenerate thyroid function in a murine model of hypothyroidism.
A study has shown that tissue-engineered colon derived from human cells is able to develop the many specialized nerves required for function, mimicking the neuronal population found in native colon. These specialized neurons, localized in the gut, form the enteric nervous system, which regulates digestive tract motility, secretion, absorption and gastrointestinal blood flow. In healthy intestines, food is moved along the digestive tract through peristalsis - a series of wave-like contractions. Special nerve cells called ganglion cells are required for this movement, but there is also a rich mixture of other types of nerve cells. "The diversity of neuron types that grew within the human tissue-engineered colon was a revelation to our team, because previously we had only documented that some ganglia were present."
If you need a working miniature brain - say for drug testing, to test neural tissue transplants, or to experiment with how stem cells work - a new paper describes how to build one with relative ease and low expense. The little balls of brain aren't performing any cogitation, but they produce electrical signals and form their own neural connections - synapses - making them readily producible testbeds for neuroscience research. Just a small sample of living tissue from a single rodent can make thousands of mini-brains. The recipe involves isolating and concentrating the desired cells with some centrifuge steps and using that refined sample to seed the cell culture in medium in an agarose spherical mold. The mini-brains, about a third of a millimeter in diameter, are not the first or the most sophisticated working cell cultures of a central nervous system, the researchers acknowledged, but they require fewer steps to make and they use more readily available materials.