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Human blood stem cells have been grown in the laboratory for the first time by researchers at Boston Children's Hospital.
Date-18/05/2017
Researchers at Boston Children's Hospital have, for the first time, generated blood-forming stem cells in the lab using pluripotent stem cells, which can make virtually every cell type in the body. The advance, published in the journal Nature, opens new avenues for research into the root causes of blood diseases and to creating immune-matched blood cells for treatment purposes, derived from patients' own cells.
"We're tantalisingly close to generating bona fide human blood stem cells in a dish," says senior investigator George Daley, PhD, who heads a research lab in Boston Children's Hospital's Stem Cell Program and is dean of Harvard Medical School. "This work is the culmination of over 20 years of striving."
"This is a very big deal," said Carolina Guibentif at the University of Cambridge, who was not involved in the research. "If you can develop [these cells] in the lab in a safe way and in high enough numbers, you wouldn't be dependent on donors."
Although the cells made from the pluripotent stem cells are a mix of true blood stem cells and other cells known as blood progenitor cells, they proved capable of generating multiple types of human blood cells when put into mice.
"This step opens up an opportunity to take cells from patients with genetic blood disorders, use gene editing to correct their genetic defect and make functional blood cells," comments Ryohichi (Rio) Sugimura, PhD, the paper's first author. "This also gives us the potential to have a limitless supply of blood stem cells and blood by taking cells from universal donors. This could potentially augment the blood supply for patients who need transfusions."
Since human embryonic stem (ES) cells were first isolated in 1998, scientists have been trying, with little success, to use them to make blood-forming stem cells. During 2007, three groups (including the Daley lab) generated the first induced pluripotent stem (iPS) cells from human skin cells through genetic reprogramming. iPS cells were later used to generate multiple human cell types, such as neurons and heart cells – yet blood-forming stem cells remained elusive.
Sugimura, Daley and colleagues combined two previous approaches. First, they exposed human pluripotent stem cells (both ES and iPS cells) to chemical signals that direct stem cells to differentiate into specialised cells and tissues during normal embryonic development. This generated hemogenic endothelium, an early embryonic tissue that eventually gives rise to blood stem cells, although the transition to blood stem cells had never been achieved in a dish.
In the second step, the team added genetic regulatory factors (called transcription factors) to push the hemogenic endothelium toward a blood-forming state. Starting with 26 transcription factors identified as likely candidates, they eventually came down to just five (RUNX1, ERG, LCOR, HOXA5 and HOXA9) that were both necessary and sufficient for creating blood stem cells. They delivered the factors into the cells with a lentivirus, as used in some forms of gene therapy.
Finally, they transplanted the genetically engineered hemogenic endothelial cells into mice. Weeks later, a small number of the animals carried multiple types of human blood cells in their bone marrow and blood circulation. These included red blood cell precursors, myeloid cells (precursors of monocytes, macrophages, neutrophils, platelets and other cells), and T and B lymphocytes. Some mice were able to mount a human immune response after vaccination.
ES cells and iPS cells were similarly good at creating blood stem and progenitor cells when the technique was applied. But the researchers are most interested in iPS cells, which offer the added ability to derive cells directly from patients and model disease.
"We're now able to model human blood function in so-called 'humanised mice,'" says Daley. "This is a major step forward for our ability to investigate genetic blood disease."
One challenge in making bona-fide human blood stem cells is that no one's been able to fully characterise them: "It's proved challenging to 'see' these cells," says Sugimura. "You can roughly characterise blood stem cells based on surface markers, but even with this, it may not be a true blood stem cell. And once it starts to differentiate and make blood cells, you can't go back and study it – it's already gone. A better characterisation of human blood stem cells and a better understanding of how they develop would give us clues to making bona-fide human blood stem cells."
5th May 2017
The first synthetic retina using soft biological tissues has been created by a student at the University of Oxford.
Credit: Oxford University
A synthetic, soft tissue retina developed by an Oxford University student could offer fresh hope to visually impaired people. Until now, all artificial retinal research has used only rigid, hard materials. However, new research by Vanessa Restrepo-Schild, a 24-year-old Dphil student and researcher at Oxford University's Department of Chemistry, is the first to successfully use biological, synthetic tissues, developed in a laboratory. The study could revolutionise the bionic implant industry and the development of new, less invasive technologies that more closely resemble human body tissues, helping to treat degenerative eye conditions.
Just as photography depends on camera pixels reacting to light, our vision relies on the retina performing the same function. The retina sits at the back of the human eye, and contains protein cells that convert light into electrical signals that travel through the nervous system, triggering a response from the brain, ultimately building a picture of the scene being viewed.
Restrepo-Schild led the team in developing a new synthetic, double layered retina that closely mimics the natural human retinal process. The retina replica consists of soft water droplets (hydrogels) and biological cell membrane proteins. Designed like a camera, the cells act as pixels, detecting and reacting to light to create a greyscale image. Restrepo-Schild explains: "The synthetic material can generate electrical signals, which stimulate the neurons at the back of our eye – just like the original retina."
The study, published in Scientific Reports, shows that unlike existing artificial retinal implants, the cell cultures are created from natural, biodegradable materials and do not contain foreign bodies or living entities. In this way, the implant is less invasive than a mechanical device, and is less likely to have an adverse reaction on the body. Miss Restrepo-Schild adds: "The human eye is incredibly sensitive, which is why foreign bodies like metal retinal implants can be so damaging – leading to inflammation and/or scarring. But a biological synthetic implant is soft and water based, so much more friendly to the eye environment."
Of the motivation behind her ground-breaking study, Miss Restrepo-Schild says: "I have always been fascinated by the human body, and want to prove that current technology could be used to replicate the function of human tissues, without having to actually use living cells.
"I have taken the principals behind vital bodily functions, e.g. our sense of hearing, touch and the ability to detect light, and replicated them in a laboratory environment with natural, synthetic components. I hope my research is the first step in a journey towards building technology that is soft and biodegradable instead of hard and wasteful."
Although at present the synthetic retina has only been tested in laboratory conditions, Miss Restrepo-Schild is keen to build on her initial work and explore potential uses with living tissues. This next step is vital in demonstrating how the material performs as a bionic implant.
Restrepo-Schild has filed a patent for the technology and the next phase of work will expand the replica's function to include recognising colours and potentially even shapes and symbols. Looking further ahead, the team will begin to include animal testing and then a series of clinical trials in humans.
3rd May 2017
The University of Utah has revealed a new robotic drill system for greatly speeding up surgical procedures. One type of complex cranial surgery could be done in a fiftieth of the normal time, decreasing from two hours to just two and a half minutes.
A computer-driven automated drill, similar to those used to machine auto parts, could play a pivotal role in future surgical procedures. The new machine can make one type of complex cranial surgery 50 times faster than standard procedures, decreasing from two hours to two and a half minutes. Researchers at the University of Utah developed a drill that produces fast, clean and safe cuts – reducing the time the wound is open and the patient is anesthetised, thereby decreasing the incidence of infection, human error, and surgical cost. The findings are reported in Neurosurgical Focus.
To perform complex surgeries – especially cranial surgeries – surgeons typically use hand drills to make intricate openings, adding hours to a procedure: "It was like doing archaeology," said William Couldwell, study author and neurosurgeon at the University of Utah Health. "We had to slowly take away the bone to avoid sensitive structures."
Couldwell saw a need for a device that could alleviate this burden and make the process more efficient: "We knew the technology was already available in the machine world, but no one ever applied it to medical applications."
"My expertise is dealing with the removal of metal quickly, so a neurosurgical drill was a new concept for me," explained A. K. Balaji, associate professor in mechanical engineering. "I was interested in developing a low-cost drill that could do a lot of the grunt work to reduce surgeon fatigue."
Credit: University of Utah
The team developed the drill from scratch, as well as new software to calculate the safest cutting path. First, the patient is imaged using CT scans to gather bone data and identify the exact location of sensitive structures, such as nerves, veins and arteries that must be avoided. Surgeons then use this information to program a cutting path for the drill: "The software lets the surgeon choose the optimum path from point A to point B, like Google Maps," says Balaji. In addition, the surgeon can program safety barriers along the cutting path within 1 mm of sensitive structures. "Think of the barriers like a construction zone," says Balaji. "You slow down to navigate it safety."
The translabyrinthine surgery is performed thousands of times a year to expose slow-growing, benign tumours that can form at auditory nerves. This cut must avoid several sensitive features, including facial nerves and the venous sinus, a large vein that drains blood from the brain. Risks of this surgery include loss of facial movement. The system developed at Utah has an automatic emergency shut-off switch. During surgery, facial nerves are monitored for any signs of irritation: "If the drill gets too close to the facial nerve and irritation is monitored, the drill automatically turns off," says Couldwell.
The new drill could reduce the duration of this complex procedure from two hours for hand-drilling by an experienced surgeon to two and a half minutes. The shorter surgery is expected to lower the chance of infection and improve post-operative recovery. It also has potential to substantially reduce the cost of surgery, because it shaves hours from operating room time.
The team has now demonstrated the safety and speed of the drill by performing this complex cut – but Couldwell stresses that it can be applied to many other procedures: "This drill can be used for a variety of surgeries, like machining the perfect receptacle opening in the bone for a hip implant," he said.
The varied application of the drill highlights another factor that drew Balaji to the project: "I was motivated by the fact that this technology could democratise health care by levelling the playing field so more people can receive quality care," he said. The team is now examining opportunities to commercialise the drill to ensure that it is more widely available for other surgical procedures.
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Light rays from a supernova bent by the curvature of space-time around a galaxy
Date:April 20, 2017 Summary:Astronomers have detected for the first time multiple images from a gravitationally lensed Type Ia supernova. The new observations suggest promising new avenues for the study of the accelerated expansion of the universe, gravity and distribution of dark matter in the universe FULL STORY The light from the supernova iPTF16geu and of its host galaxy is warped and amplified by the curvature of space mass of a foreground galaxy. In the case of the point-like supernova, the light is split into four images. These have been resolved with the Hubble Space Telescope. Credit: Original image by ALMA (ESO/NRAO/NAOJ), L. Calçada (ESO), Y. Hezaveh et al, edited and modified by Joel Johansson An international research team led by Ariel Goobar at Stockholm University has detected for the first time multiple images from a gravitationally lensed Type Ia supernova. The new observations suggest promising new avenues for the study of the accelerated expansion of the Univer...
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