As reported online Oct. 2, 2019, by Molecular Cell, a Harvard team was able to use the gene editing tool CRISPR to kill certain viruses, including the influenza virus, in a laboratory dish.
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 cells, 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 infected cell. 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 chimeric antigen receptor, 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.”
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 stem cells. Organoids promise to cut down on the need for animal testing 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.
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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.
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 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 today, 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 lymphocytes.
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.
A large project is underway to disease-proof pigs using CRISPR to change their DNA. Are people next?
Finding alternatives to antibiotics is one of the biggest challenges facing the research community. Bacteria are increasingly resistant to these drugs, and this resistance leads to the deaths of more than 25,000 around the world. Now, a multidisciplinary team of researchers from the Universitat Rovira i Virgili, the University of Grenoble (France), the University of Saarland (Germany) and RMIT University (Australia) have discovered that the mechanical deformation of bacteria is a toxic mechanism that can kill bacteria with gold nanoparticles. The results of this research have been published in the journal Advanced Materials and are a breakthrough in researchers’ understanding the antibacterial effects of nanoparticles and their efforts to find new materials with bactericide properties.
Since the times of Ancient Egypt, gold has been used in a range of medical applications and, more recently, as for diagnosing and treating diseases such as cancer. This is due to the fact that gold is a chemically inert material, that is, it does not react or change when it comes into contact with an organism. Amongst the scientific community, nanoparticles are known for their ability to make tumors visible and for their applications in nanomedicine.
This new research shows that these chemically inert nanoparticles can kill bacteria thanks to a physical mechanism that deforms the cell wall. To demonstrate this, the researchers have synthesized in the laboratory gold nanoparticles in the shape of an almost perfect sphere and others in the shape of stars, all measuring 100 nanometres (8 times thinner than a hair). The group analyzed how these particle interact with living bacteria. “We find that the bacteria become deformed and deflate like a ball that is having the air let out before dying in the presence of these nanoparticles,” explained Vladimir Baulin, researcher at the Department of Chemical Engineering of the URV. The researchers state the bacteria seem to have died after a massive leak, “as if the cell wall had spontaneously exploded.”
Dr yu shrike zhang phd is assistant professor at harvard medical school and associate bioengineer at brigham and women’s hospital.
Dr. Zhang’s research interests include symbiotic tissue engineering, 3D bio-printing, organ-on-a-chip technology, biomaterials, regenerative engineering, bioanalysis, nanomedicine, and biology.
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