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Category: bioengineering – Page 104

Honorable Mentions

One more scientific brilliance this year is the use of light in neuroscience and tissue engineering. One study, for example, used lasers to directly print a human ear-like structure under the skin of mice, without a single surgical cut. Another used light to incept smell in mice, artificially programming an entirely new, never-seen-in-nature perception of a scent directly into their brains. Yet another study combined lasers with virtual reality to dissect how our brains process space and navigation, “mentally transporting” a mouse to a virtual location linked to a reward. To cap it off, scientists found a new way to use light to control the brain through the skull without surgery—though as of now, you’ll still need gene therapy. Given the implications of unauthorized “mind control,” that’s probably less of a bug and more of a feature.

We’re nearing the frustratingly slow, but sure, dying gasp of Covid-19. The pandemic defined 2020, but science kept hustling along. I can’t wait to share what might come in the next year with you—may it be revolutionary, potentially terrifying, utterly bizarre or oddly heart-warming.

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A new study has found that a novel T cell genetically engineered by University of Arizona Health Sciences researchers is able to target and attack pathogenic T cells that cause Type 1 diabetes, which could lead to new immunotherapy treatments.

The immune system fights bacteria, viruses and other pathogens by utilizing several types of T , all of which have receptors that are specific to particular antigens. On killer T cells, the receptor works in concert with three signaling modules and a coreceptor to destroy the . Michael Kuhns, Ph.D., an associate professor in the UArizona College of Medicine—Tucson Department of Immunobiology, copied the evolutionary design to engineer a five-module , or 5MCAR, T cell.

“The 5MCAR was an attempt to figure out if we could build something by biomimicry, using some of evolution’s natural pieces, and redirect T cells to do what we want them to do. We engineered a 5MCAR that would direct killer T cells to target autoimmune T cells that mediate Type 1 diabetes,” said Dr. Kuhns, who is member of the UArizona Cancer Center, BIO5 Institute and Arizona Center on Aging. “So now, a killer T cell will actually recognize another T cell. We flipped T cell-mediated immunity on its head.”

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Researchers at EPFL have developed an approach to print tiny tissues that look and function almost like their full-sized counterpart. Measuring just a few centimeters across, the mini-tissues could allow scientists to study biological processes—and even test new treatment approaches—in ways that were previously not possible.

For years, mini versions of organs such as the brain, kidney and lung—known as “organoids”—have been grown from . Organoids promise to cut down on the need for and offer better models to study how human organs form and how that process goes awry in disease. However, conventional approaches to grow organoids result in stem cells assembling into micro-to millimeter-sized, hollow spheres. “That is non-physiological, because many organs, such as the intestine or the airway, are tube-shaped and much larger,” says Matthias Lütolf, a professor at EPFL’s Institute of Bioengineering, who led the study published today in Nature Materials.

To develop larger organoids that resemble their normal counterparts, Lütolf and his team turned to bioprinting. Just as 3D-printers allow people to create everyday objects, similar technology can help bioengineers to assemble living tissues. But instead of the plastics or powders used in conventional 3D-printers, bioprinters use bioinks—liquids or gels that encapsulate living cells. “Bioprinting is very compelling because it allows you to deposit cells anywhere in 3D space, so you could think of arranging cells into an organ-like configuration such as a tube,” Lütolf says.

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Researchers from the Francis Crick Institute (FCI) and University College London (UCL) have rebuilt a human thymus, an essential organ of the immune system, using human stem cells and a bioengineered scaffold. Their work is an important step towards being able to grow artificial thymi for use as transplants.

The thymus – located in the upper front part of the chest, behind the sternum – is a lymphoid organ where T cells mature. These play a vital role in the body’s immune system. If the thymus does not work properly or does not form during foetal development in the womb, it can result in severe immunodeficiency and other conditions where the body cannot fight infectious diseases or cancerous cells, or autoimmunity, where the immune system mistakenly attacks the patient’s own healthy tissue.

In their proof-of-concept study, published in Nature Communications, the scientists rebuilt thymi using stem cells taken from patients who had to have the organ removed during surgery. When transplanted into mice, the bioengineered thymi were able to support the development of mature and functional human T cells.

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Researchers at the Francis Crick Institute and University College London have rebuilt a human thymus, an essential organ in the immune system, using human stem cells and a bioengineered scaffold. Their work is an important step towards being able to build artificial thymi which could be used as transplants.

The thymus is an organ in the chest where T lymphocytes, which play a vital role in the immune system, mature. If the thymus does not work properly or does not form during foetal development in the womb, this can lead to diseases such as severe immunodeficiency, where the body cannot fight infectious diseases or , or autoimmunity, where the immune system mistakenly attacks the patient’s own healthy tissue.

In their proof-of-concept study, published in Nature Communications today, the scientists rebuilt thymi using taken from patients who had to have the organ removed during surgery. When transplanted into mice, the bioengineered thymi were able to support the development of mature and functional human T lymphocytes.

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Takeaways * Scientists have made progress growing human liver in the lab. * The challenge has been to direct stems cells to grow into a mature, functioning adult organ. * This study shows that stem cells can be programmed, using genetic engineering, to grow from immature cells into mature tissue. * When a tiny lab-grown liver was transplanted into mice with liver disease, it extended the lives of the sick animals.* * *Imagine if researchers could program stem cells, which have the potential to grow into all cell types in the body, so that they could generate an entire human organ. This would allow scientists to manufacture tissues for testing drugs and reduce the demand for transplant organs by having new ones grown directly from a patient’s cells. I’m a researcher working in this new field – called synthetic biology – focused on creating new biological parts and redesigning existing biological systems. In a new paper, my colleagues and I showed progress in one of the key challenges with lab-grown organs – figuring out the genes necessary to produce the variety of mature cells needed to construct a functioning liver. Induced pluripotent stem cells, a subgroup of stem cells, are capable of producing cells that can build entire organs in the human body. But they can do this job only if they receive the right quantity of growth signals at the right time from their environment. If this happens, they eventually give rise to different cell types that can assemble and mature in the form of human organs and tissues. The tissues researchers generate from pluripotent stem cells can provide a unique source for personalized medicine from transplantation to novel drug discovery. But unfortunately, synthetic tissues from stem cells are not always suitable for transplant or drug testing because they contain unwanted cells from other tissues, or lack the tissue maturity and a complete network of blood vessels necessary for bringing oxygen and nutrients needed to nurture an organ. That is why having a framework to assess whether these lab-grown cells and tissues are doing their job, and how to make them more like human organs, is critical. Inspired by this challenge, I was determined to establish a synthetic biology method to read and write, or program, tissue development. I am trying to do this using the genetic language of stem cells, similar to what is used by nature to form human organs. Tissues and organs made by genetic designsI am a researcher specializing in synthetic biology and biological engineering at the Pittsburgh Liver Research Center and McGowan Institute for Regenerative Medicine, where the goals are to use engineering approaches to analyze and build novel biological systems and solve human health problems. My lab combines synthetic biology and regenerative medicine in a new field that strives to replace, regrow or repair diseased organs or tissues. I chose to focus on growing new human livers because this organ is vital for controlling most levels of chemicals – like proteins or sugar – in the blood. The liver also breaks down harmful chemicals and metabolizes many drugs in our body. But the liver tissue is also vulnerable and can be damaged and destroyed by many diseases, such as hepatitis or fatty liver disease. There is a shortage of donor organs, which limits liver transplantation. To make synthetic organs and tissues, scientists need to be able to control stem cells so that they can form into different types of cells, such as liver cells and blood vessel cells. The goal is to mature these stem cells into miniorgans, or organoids, containing blood vessels and the correct adult cell types that would be found in a natural organ. One way to orchestrate maturation of synthetic tissues is to determine the list of genes needed to induce a group of stem cells to grow, mature and evolve into a complete and functioning organ. To derive this list I worked with Patrick Cahan and Samira Kiani to first use computational analysis to identify genes involved in transforming a group of stem cells into a mature functioning liver. Then our team led by two of my students – Jeremy Velazquez and Ryan LeGraw – used genetic engineering to alter specific genes we had identified and used them to help build and mature human liver tissues from stem cells. The tissue is grown from a layer of genetically engineered stem cells in a petri dish. The function of genetic programs together with nutrients is to orchestrate formation of liver organoids over the course of 15 to 17 days. Liver in a dishI and my colleagues first compared the active genes in fetal liver organoids we had grown in the lab with those in adult human livers using a computational analysis to get a list of genes needed for driving fetal liver organoids to mature into adult organs. We then used genetic engineering to tweak genes – and the resulting proteins – that the stem cells needed to mature further toward an adult liver. In the course of about 17 days we generated tiny – several millimeters in width – but more mature liver tissues with a range of cells typically found in livers in the third trimester of human pregnancies. Like a mature human liver, these synthetic livers were able to store, synthesize and metabolize nutrients. Though our lab-grown livers were small, we are hopeful that we can scale them up in the future. While they share many similar features with adult livers, they aren’t perfect and our team still has work to do. For example, we still need to improve the capacity of the liver tissue to metabolize a variety of drugs. We also need to make it safer and more efficacious for eventual application in humans.[Deep knowledge, daily. Sign up for The Conversation’s newsletter.]Our study demonstrates the ability of these lab livers to mature and develop a functional network of blood vessels in just two and a half weeks. We believe this approach can pave the path for the manufacture of other organs with vasculature via genetic programming. The liver organoids provide several key features of an adult human liver such as production of key blood proteins and regulation of bile – a chemical important for digestion of food. When we implanted the lab-grown liver tissues into mice suffering from liver disease, it increased the life span. We named our organoids “designer organoids,” as they are generated via a genetic design. This article is republished from The Conversation, a nonprofit news site dedicated to sharing ideas from academic experts. It was written by: Mo Ebrahimkhani, University of Pittsburgh. Read more: * Brain organoids help neuroscientists understand brain development, but aren’t perfect matches for real brains * Why are scientists trying to manufacture organs in space?Mo Ebrahimkhani receives funding from National Institute of Health, University of Pittsburgh and Arizona Biomedical Research Council.

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