Stem Cell Clinic

Team builds the 1st living robots – EarthSky

By Embryonic Stem Cells

Scientists from the University of Vermont (UVM) and Tufts University in Massachusetts said on January 13, 2020, that theyve now assembled living cells into entirely new life-forms. They call them living robots, or xenobots for the frog species from whose cells the little robots sprang. The scientists describe them as tiny blobs, submillimeter in size (a millimeter is about 1/25th of an inch, so these little blobs are smaller than that). The blobs contain between 500 and 1,000 cells. They can heal themselves after being cut. The blobs have been able to scoot across a petri dish, self-organize, and even transport minute payloads. Maybe, eventually, theyll be able to carry a medicine to a specific place inside a human body, scrape plaque from arteries, search out radioactive contamination, or gather plastic pollution in Earths oceans.

And, yes, the scientists do acknowledge possible ethical issues. More about that below.

Joshua Bongard, a computer scientist and robotics expert at the University of Vermont who co-led the new research, said in a statement:

These are novel living machines. Theyre neither a traditional robot nor a known species of animal. Its a new class of artifact: a living, programmable organism

You look at the cells weve been building our xenobots with, and, genomically, theyre frogs. Its 100% frog DNA but these are not frogs. Then you ask, well, what else are these cells capable of building?

The results of the new research were published January 13 in the Proceedings of the National Academy of Sciences.

EarthSky 2020 lunar calendars are available! Only a few left. Order now!

A manufactured quadruped (4-footed) organism, 650-750 microns in diameter (a micron is a millionth of a meter). The scientists described this creature (if we can call it a creature) as a bit smaller than a pinhead. Image via Douglas Blackiston/ Tufts University/ University of Vermont.

In their published paper, these scientists wrote:

Most technologies are made from steel, concrete, chemicals, and plastics, which degrade over time and can produce harmful ecological and health side effects. It would thus be useful to build technologies using self-renewing and biocompatible materials, of which the ideal candidates are living systems themselves. Thus, we here present a method that designs completely biological machines from the ground up: computers automatically design new machines in simulation, and the best designs are then built by combining together different biological tissues. This suggests others may use this approach to design a variety of living machines to safely deliver drugs inside the human body, help with environmental remediation, or further broaden our understanding of the diverse forms and functions life may adopt.

The new creatures were designed on a supercomputer at UVM, and then assembled and tested by biologists at Tufts University. The scientists statement described their process this way:

With months of processing time on the Deep Green supercomputer cluster at UVMs Vermont Advanced Computing Core, the team including lead author and doctoral student Sam Kriegman of UVM [@Kriegmerica on Twitter] used an evolutionary algorithm to create thousands of candidate designs for the new life-forms. Attempting to achieve a task assigned by the scientists like locomotion in one direction the computer would, over and over, reassemble a few hundred simulated cells into myriad forms and body shapes. As the programs ran driven by basic rules about the biophysics of what single frog skin and cardiac cells can do the more successful simulated organisms were kept and refined, while failed designs were tossed out. After a hundred independent runs of the algorithm, the most promising designs were selected for testing.

Then the team at Tufts, led by Michael Levin and with key work by microsurgeon Douglas Blackiston transferred the in-silico designs into life. First they gathered stem cells, harvested from embryos of African frogs, the species Xenopus laevis [African clawed frogs; hence the name xenobots.]

These were separated into single cells and left to incubate. Then, using tiny forceps and an even tinier electrode, the cells were cut and joined under a microscope into a close approximation of the designs specified by the computer.

Assembled into body forms never seen in nature, the cells began to work together. The skin cells formed a more passive architecture, while the once-random contractions of heart muscle cells were put to work creating ordered forward motion as guided by the computers design, and aided by spontaneous self-organizing patterns allowing the robots to move on their own.

These reconfigurable organisms were shown to be able move in a coherent fashion and explore their watery environment for days or weeks, powered by embryonic energy stores. Turned over, however, they failed, like beetles flipped on their backs.

Later tests showed that groups of xenobots would move around in circles, pushing pellets into a central location spontaneously and collectively. Others were built with a hole through the center to reduce drag. In simulated versions of these, the scientists were able to repurpose this hole as a pouch to successfully carry an object.

Wow yes?

The scientists said they see this work as part of a bigger picture. And they acknowledged that some may fear the implications of rapid technological change and complex biological manipulations. Levin commented:

That fear is not unreasonable. When we start to mess around with complex systems that we dont understand, were going to get unintended consequences.

However, he said:

If humanity is going to survive into the future, we need to better understand how complex properties, somehow, emerge from simple rules.

He said much of science is focused on:

controlling the low-level rules. We also need to understand the high-level rules.

I think its an absolute necessity for society going forward to get a better handle on systems where the outcome is very complex. A first step towards doing that is to explore: how do living systems decide what an overall behavior should be and how do we manipulate the pieces to get the behaviors we want?

In other words, he said:

this study is a direct contribution to getting a handle on what people are afraid of, which is unintended consequences.

Bongard added:

Theres all of this innate creativity in life. We want to understand that more deeply and how we can direct and push it toward new forms.

On the left, the anatomical blueprint for a computer-designed organism, discovered on a UVM supercomputer. On the right, the living organism, built entirely from frog skin (green) and heart muscle (red) cells. The background displays traces carved by a swarm of these new-to-nature organisms as they move through a field of particulate matter. Image via Sam Kriegman/ UVM.

Bottom line: Scientists said in early January 2020 that theyve created the first living robots, or xenobots, assembled from the cells of frogs. Their creators promise advances from drug delivery to toxic waste clean-up.

Source: A scalable pipeline for designing reconfigurable organisms

Via UVM

Read this article:
Team builds the 1st living robots - EarthSky

Team Builds the First Living Robots – Newswise

By Embryonic Stem Cells

MEDIA CONTACT

Available for logged-in reporters only

Research Results

SCIENCE

Newswise A book is made of wood. But it is not a tree. The dead cells have been repurposed to serve another need.

Now a team of scientists has repurposed living cells--scraped from frog embryos--and assembled them into entirely new life-forms. These millimeter-wide "xenobots" can move toward a target, perhaps pick up a payload (like a medicine that needs to be carried to a specific place inside a patient)--and heal themselves after being cut.

"These are novel living machines," saysJoshua Bongard, a computer scientist and robotics expert at the University of Vermont who co-led the new research. "They're neither a traditional robot nor a known species of animal. It's a new class of artifact: a living, programmable organism."

The new creatures were designed on a supercomputer at UVM--and then assembled and tested by biologists at Tufts University. "We can imagine many useful applications of these living robots that other machines can't do," says co-leader Michael Levin who directs theCenter for Regenerative and Developmental Biologyat Tufts, "like searching out nasty compounds or radioactive contamination, gathering microplastic in the oceans, traveling in arteries to scrape out plaque."

The results of the new research were published January 13 in theProceedings of the National Academy of Sciences.

BESPOKE LIVING SYSTEMS

People have been manipulating organisms for human benefit since at least the dawn of agriculture, genetic editing is becoming widespread, and a few artificial organisms have been manually assembled in the past few years--copying the body forms of known animals.

But this research, for the first time ever, "designs completely biological machines from the ground up," the team writes in their new study.

With months of processing time on the Deep Green supercomputer cluster at UVM'sVermont Advanced Computing Core, the team--including lead author and doctoral student Sam Kriegman--used an evolutionary algorithm to create thousands of candidate designs for the new life-forms. Attempting to achieve a task assigned by the scientists--like locomotion in one direction--the computer would, over and over, reassemble a few hundred simulated cells into myriad forms and body shapes. As the programs ran--driven by basic rules about the biophysics of what single frog skin and cardiac cells can do--the more successful simulated organisms were kept and refined, while failed designs were tossed out. After a hundred independent runs of the algorithm, the most promising designs were selected for testing.

Then the team at Tufts, led by Levin and with key work by microsurgeon Douglas Blackiston--transferred the in silico designs into life. First they gathered stem cells, harvested from the embryos of African frogs, the speciesXenopus laevis. (Hence the name "xenobots.") These were separated into single cells and left to incubate. Then, using tiny forceps and an even tinier electrode, the cells were cut and joined under a microscope into a close approximation of the designs specified by the computer.

Assembled into body forms never seen in nature, the cells began to work together. The skin cells formed a more passive architecture, while the once-random contractions of heart muscle cells were put to work creating ordered forward motion as guided by the computer's design, and aided by spontaneous self-organizing patterns--allowing the robots to move on their own.

These reconfigurable organisms were shown to be able move in a coherent fashion--and explore their watery environment for days or weeks, powered by embryonic energy stores. Turned over, however, they failed, like beetles flipped on their backs.

Later tests showed that groups of xenobots would move around in circles, pushing pellets into a central location--spontaneously and collectively. Others were built with a hole through the center to reduce drag. In simulated versions of these, the scientists were able to repurpose this hole as a pouch to successfully carry an object. "It's a step toward using computer-designed organisms for intelligent drug delivery," says Bongard, a professor in UVM'sDepartment of Computer ScienceandComplex Systems Center.

LIVING TECHNOLOGIES

Many technologies are made of steel, concrete or plastic. That can make them strong or flexible. But they also can create ecological and human health problems, like the growing scourge of plastic pollution in the oceans and the toxicity of many synthetic materials and electronics. "The downside of living tissue is that it's weak and it degrades," say Bongard. "That's why we use steel. But organisms have 4.5 billion years of practice at regenerating themselves and going on for decades." And when they stop working--death--they usually fall apart harmlessly. "These xenobots are fully biodegradable," say Bongard, "when they're done with their job after seven days, they're just dead skin cells."

Your laptop is a powerful technology. But try cutting it in half. Doesn't work so well. In the new experiments, the scientists cut the xenobots and watched what happened. "We sliced the robot almost in half and it stitches itself back up and keeps going," says Bongard. "And this is something you can't do with typical machines."

CRACKING THE CODE

Both Levin and Bongard say the potential of what they've been learning about how cells communicate and connect extends deep into both computational science and our understanding of life. "The big question in biology is to understand the algorithms that determine form and function," says Levin. "The genome encodes proteins, but transformative applications await our discovery of how that hardware enables cells to cooperate toward making functional anatomies under very different conditions."

To make an organism develop and function, there is a lot of information sharing and cooperation--organic computation--going on in and between cells all the time, not just within neurons. These emergent and geometric properties are shaped by bioelectric, biochemical, and biomechanical processes, "that run on DNA-specified hardware," Levin says, "and these processes are reconfigurable, enabling novel living forms."

The scientists see the work presented in their newPNASstudy--"A scalable pipeline for designing reconfigurable organisms,"--as one step in applying insights about this bioelectric code to both biology and computer science. "What actually determines the anatomy towards which cells cooperate?" Levin asks. "You look at the cells we've been building our xenobots with, and, genomically, they're frogs. It's 100% frog DNA--but these are not frogs. Then you ask, well, what else are these cells capable of building?"

"As we've shown, these frog cells can be coaxed to make interesting living forms that are completely different from what their default anatomy would be," says Levin. He and the other scientists in the UVM and Tufts team--with support from DARPA's Lifelong Learning Machines program and the National Science Foundation-- believe that building the xenobots is a small step toward cracking what he calls the "morphogenetic code," providing a deeper view of the overall way organisms are organized--and how they compute and store information based on their histories and environment.

FUTURE SHOCKS

Many people worry about the implications of rapid technological change and complex biological manipulations. "That fear is not unreasonable," Levin says. "When we start to mess around with complex systems that we don't understand, we're going to get unintended consequences." A lot of complex systems, like an ant colony, begin with a simple unit--an ant--from which it would be impossible to predict the shape of their colony or how they can build bridges over water with their interlinked bodies.

"If humanity is going to survive into the future, we need to better understand how complex properties, somehow, emerge from simple rules," says Levin. Much of science is focused on "controlling the low-level rules. We also need to understand the high-level rules," he says. "If you wanted an anthill with two chimneys instead of one, how do you modify the ants? We'd have no idea."

"I think it's an absolute necessity for society going forward to get a better handle on systems where the outcome is very complex," Levin says. "A first step towards doing that is to explore: how do living systems decide what an overall behavior should be and how do we manipulate the pieces to get the behaviors we want?"

In other words, "this study is a direct contribution to getting a handle on what people are afraid of, which is unintended consequences," Levin says--whether in the rapid arrival of self-driving cars, changing gene drives to wipe out whole lineages of viruses, or the many other complex and autonomous systems that will increasingly shape the human experience.

"There's all of this innate creativity in life," says UVM's Josh Bongard. "We want to understand that more deeply--and how we can direct and push it toward new forms."

###

SEE ORIGINAL STUDY

Read the original here:
Team Builds the First Living Robots - Newswise

The ‘xenobot’ is the worlds newest robot and it’s made from living animal cells – The Loop

By Embryonic Stem Cells

Forget gleaming metal droids -- the robots of the future may have more in common with the average amphibian than with R2D2.

A team of scientists have found a way to not just program a living organism, but to build brand new life-forms from scratch using cells, creating what researchers are calling xenobots.

Tiny in size, but vast in potential, these millimetre-sized bots could potentially be programmed to help in medical procedures, ocean cleanup and investigating dangerous compounds, among other things.

"They're neither a traditional robot nor a known species of animal, said researcher Joshua Bongard in a news release. It's a new class of artifact: a living, programmable organism."

In the introduction for the research published in Proceedings of the National Academy of Sciences (PNAS) on Monday, researchers point out that the traditional building blocks weve used for robots and tech -- steel, plastic, chemicals, etc. -- all degrade over time and can produce harmful ecological and health side-effects.

After realizing that the best self-renewing and biocompatible materials would be living systems themselves, researchers decided to create a method that designs completely biological machines from the ground up.

The bots are made out of stem cells taken from frog embryos -- specifically, an African clawed frog called xenopus laevis, which supplied the inspiration for the name xenobot. To design the xenobots, the possible configurations of different cells were first modeled on a supercomputer at the University of Vermont.

The designs then went to Tufts University, where the embryonic cells were collected and separated to develop into more specialized cells. Then, like sculptors (if sculptors used microsurgery forceps and electrodes), biologists manually shaped the cells into clumps that matched the computer designs.

Different structures were sketched out by the computer in accordance with the scientists goal for each xenobot.

For example, one xenobot was designed to be able to move purposely in a specific direction. To achieve this, researchers put cardiac cells on the bottom of the xenobot. These cells naturally contract and expand on their own, meaning that they could serve as the xenobots engine, or legs, and help move the rest of the organism, which was built out of more static skin cells.

In order to test if the living robots were truly moving the way they were designed to, and not just randomly, researchers performed a test that has stumped many a living creature.

They flipped the robot on its back. And just like a capsized turtle, it could no longer move.

When researchers created further designs for the bots, they found that they could design them to push microscopic objects, and even carry objects through a pouch.

"It's a step toward using computer-designed organisms for intelligent drug delivery," says Bongard.

The possible uses for these tiny robots are numerous, researchers say.

In biomedical settings, one could envision such biobots (made from the patients own cells) removing plaque from artery walls, identifying cancer, or settling down to differentiate or control events in locations of disease, the research paper suggests.

A robot made out of metal or steel generally has to be repaired by human hands if it sustains damage. One major benefit that researchers found of creating these robots out of living cells was how they reacted to physical damage.

A video taken by the researchers showed that when one of their organisms was cut almost in half by metal tweezers, the two sides of the wound simply stitched itself back together.

These living robots, researchers realized, could repair themselves automatically, something you cant do with typical machines, Bongard said.

Because they are living cells, they are also naturally biodegradable, Bongard pointed out. Once theyve fulfilled their purpose, theyre just dead skin cells, making them even more optimal for usage in medical or environmental research.

Although scientists have been increasingly manipulating genetics and biology, this is the first time that a programmable organism has been created from scratch, researchers say.

This new research takes scientists a step closer to answering just how different cells work together to execute all of the complex processes that occur every day in animals and humans.

"The big question in biology is to understand the algorithms that determine form and function," said co-leader Michael Levin in the press release. He directs the Center for Regenerative and Developmental Biology at Tufts.

"What actually determines the anatomy towards which cells co-operate? he asked. You look at the cells we've been building our xenobots with, and, genomically, they're frogs. It's 100 per cent frog DNA -- but these are not frogs. Then you ask, well, what else are these cells capable of building? As we've shown, these frog cells can be coaxed to make interesting living forms that are completely different from what their default anatomy would be.

Of course, a biological organism created and programmed by humans which is capable of healing itself might sound a little alarming. After all, one of the sponsors of the research is the Defense Advanced Research Projects Agency, which is affiliated with the U.S. military.

Researchers acknowledged in the press release that the implications around such technological and biological advancements can be worrying at times.

That fear is not unreasonable, Levin said. However, he believes that in order to move forward with science, we should not hold back from complex questions. This study is a direct contribution to getting a handle on what people are afraid of, which is unintended consequences.

"I think it's an absolute necessity for society going forward to get a better handle on systems where the outcome is very complex," Levin says. "A first step towards doing that is to explore: how do living systems decide what an overall behavior should be and how do we manipulate the pieces to get the behaviors we want?"

More on this story from CTVNews.ca

Link:
The 'xenobot' is the worlds newest robot and it's made from living animal cells - The Loop

Zika Virus’ Key into Brain Cells ID’d, Leveraged to Block Infection and Kill Cancer Cells – UC San Diego Health

By Stem Cell Treatment

Zika virus infection can stunt neonatal brain development, a condition known as microcephaly, in which babies are born with abnormally small heads. To determine how best to prevent and treat the viral infection, scientists first need to understand how the pathogen gets inside brain cells.

Employing different approaches to answer different questions, two research teams at University of California San Diego School of Medicine independently identified the same molecule v5 integrin as Zika virus key to entering brain stem cells.

In a pair of papers published January 16, 2020 by Cell Press, the researchers also found ways to take advantage of the integrin to both block Zika virus from infecting cells and turn it into something good: a way to shrink brain cancer stem cells.

Integrins are molecules embedded in cell surfaces. They play important roles in cell adherence and communication, and are known to be involved in cancer progression and metastasis. Several other integrins are known entry points for other viruses, including adenovirus, foot-and-mouth disease virus and rotavirus, but v5 was not previously known for its role in viral infections.

One team, led by Tariq Rana, PhD, professor and chief of the Division of Genetics in the Department of Pediatrics at UC San Diego School of Medicine and Moores Cancer Center, used CRISPR gene editing to systematically delete every gene in a 3D culture of human glioblastoma (brain cancer) stem cells growing in a laboratory dish. Then they exposed each variation to Zika virus to determine which genes, and the proteins they encode, are required for the virus to enter the cells. The virus was for the first time labeled with green fluorescent protein (GFP) to allow the researchers to visualize viral entry into the cells.

3D human brain organoids. Left: normal, uninfected. Center: infected with Zika virus. Right: infected with Zika virus and treated with cilengitide, which protects the cells from destruction by the virus.

Their study, published in Cell Reports, uncovered 92 specific human brain cancer stem cell genes that Zika virus requires to infect and replicate in the cells. But one gene stood out, the one that encodes v5 integrin.

Integrins are well known as molecules that many different viruses use as doorknobs to gain entry into human cells, Rana said. I was expecting to find Zika using multiple integrins, or other cell surface molecules also used by other viruses. But instead we found Zika uses v5, which is unique. When we further examined v5 expression in brain, it made perfect sense because v5 is the only integrin member enriched in neural stem cells, which Zika preferentially infects. Therefore, we believe that v5 is the key contributor to Zikas ability to infect brain cells.

The second study, published in Cell Stem Cell, was led by Jeremy Rich, MD, professor in the Department of Medicine at UC San Diego School of Medicine and director of neuro-oncology and of the Brain Tumor Institute at UC San Diego Health. Knowing that many viruses use integrins for entry into human cells, Richs team inhibited each integrin with a different antibody to see which would have the greatest effect.

When we blocked other integrins, there was no difference. You might as well be putting water on a cell, said Rich, who is also a faculty member in the Sanford Consortium for Regenerative Medicine and Sanford Stem Cell Clinical Center at UC San Diego Health. But with v5, blocking it with an antibody almost completely blocked the ability of the virus to infect brain cancer stem cells and normal brain stem cells.

Richs team followed up by inhibiting v5 in a glioblastoma mouse model with either an antibody or by deactivating the gene that encodes it. Both approaches blocked Zika virus infection and allowed the treated mice to live longer than untreated mice. They also found that blocking the v5 integrin in glioblastoma tumor samples removed from patients during surgery blocked Zika virus infection.

Ranas team also blocked v5 in mice, treating them daily with cilengitide or SB273005, two experimental cancer drugs that target the integrin. Six days after Zika virus infection, the brains of their drug-treated mice contained half as much virus as mock-treated mice.

The neat thing is that these findings not only help advance the Zika virus research field, but also opens the possibility that we could similarly block the entry of multiple viruses that use other integrins with antibodies or small molecule inhibitors, Rana said.

Rana and team are now engineering a mouse model that lacks v5 integrin in the brain a tool that would allow them to definitively prove the molecule is necessary for Zika viral entry and replication.

Rich is a neuro-oncologist who specializes in diagnosing and treating patients with glioblastoma, a particularly aggressive and deadly type of brain tumor. When he first saw how the Zika virus shrinks brain tissue, it reminded him of what he hopes to achieve when hes treating a patient with glioblastoma. In 2017, he and collaborators published a study in which they determined that Zika virus selectively targets and kills glioblastoma stem cells, which tend to be resistant to standard treatments and are a big reason why glioblastomas recur after surgery and result in shorter patient survival rates.

Richs latest study helps account for the virus preference for glioblastoma stem cells over healthy brain cells. The v5 integrin is made up of two separate subunits v and 5. The team found that glioblastoma stem cells produce a lot of both the v subunit (associated with stem cells) and 5 subunit (associated with cancer cells). Together, these units form the v5 integrin, which, the team discovered, plays an important role in glioblastoma stem cell survival. Those high levels of v5 integrin also help explain why, in the study, glioblastoma stem cells were killed by Zika virus at much higher rates than normal stem cells or other brain cell types.

It turns out that the very thing that helps cancer cells become aggressive cancer stem cells is the same thing Zika virus uses to infect our cells, Rich said.

To see how this might play out in a more realistic model of human disease, Richs team partnered with an expert in human brain disease modeling Alysson Muotri, PhD, professor at UC San Diego School of Medicine, director of the UC San Diego Stem Cell Program and a member of the Sanford Consortium for Regenerative Medicine, and team. Pinar Mesci, PhD, a postdoctoral researcher in Muotris lab, generated a new brain tumor model, where human glioblastoma tumors were transplanted into human brain organoids, laboratory mini-brains that can be used for drug discovery. The researchers discovered that Zika virus selectively eliminates glioblastoma stem cells from the brain organoids. Inhibiting v5 integrin reversed that anti-cancer activity, further underscoring the molecules crucial role in Zika virus ability to destroy cells.

Now Richs team is partnering with other research groups to perform targeted drug studies. In addition to searching for drugs to block Zika virus, as Ranas group is doing, Rich is interested in genetic modifications to the virus that could help better target its destruction to brain cancer cells, while leaving healthy cells alone.

While we would likely need to modify the normal Zika virus to make it safer to treat brain tumors, we may also be able to take advantage of the mechanisms the virus uses to destroy cells to improve the way we treat glioblastoma, Rich said. We should pay attention to viruses. They have evolved over many years to be very good at targeting and entering specific cells in the body.

Zika virus was perhaps best known in 2015-16, when a large outbreak affected primarily Latin America, but also several other regions of the world. While that particular epidemic has passed, Zika virus has not gone away. Smaller, local outbreaks continue and this past summer, the first few cases of native Zika virus infection were recorded in Europe. Scientists warn Zika could continue to spread as climate change affects the habitat range of the mosquito that carries it. The virus can also be transmitted from pregnant mother to fetus, and via sexual contact. More than half of all people on Earth are at risk for Zika virus infection, and there is no safe and effective treatment or vaccine.

Co-authors of Ranas study, published January 16, 2020 in Cell Reports, include: Shaobo Wang, Qiong Zhang, Shashi Kant Tiwari, Gianluigi Lichinchi, Edwin H. Yau, Hui Hui, Wanyu Li, UC San Diego; and Frank Furnari, UC San Diego and Ludwig Institute for Cancer Research.

This research was funded, in part, by the National Institutes of Health (grants AI125103, CA177322, DA039562, DA046171 and DA049524).

Co-authors of Richs study, published January 16, 2020 in Cell Stem Cell, also include: Zhe Zhu, Jean A. Bernatchez, Xiuxing Wang, Hiromi I. Wettersten, Sungjun Beck, Alex E. Clark, Qiulian Wu, Sara M. Weis, Priscilla D. Negraes, Cleber A. Trujillo, Jair L. Siqueira-Neto, David A. Cheresh, UC San Diego; Ryan C. Gimple, Leo J.Y. Kim, UC San Diego and Case Western Reserve University; Simon T. Schafer, Fred H. Gage, Salk Institute for Biological Studies; Briana C. Prager, UC San Diego, Case Western Reserve University and Cleveland Clinic; Rekha Dhanwani, Sonia Sharma, La Jolla Institute for Allergy and Immunology; Alexandra Garancher, Robert J. Wechsler-Reya, Sanford Burnham Prebys Medical Discovery Institute; Stephen C. Mack, Baylor College of Medicine, Texas Childrens Hospital; Luiz O. Penalva, Childrens Cancer Research Institute; Jing Feng, Zhou Lan, Rong Zhang, Alex W. Wessel, Michael S. Diamond, Hongzhen Hu, Washington University School of Medicine; Sanjay Dhawan, and Clark C. Chen, University of Minnesota.

The research was funded, in part, by the National Institutes of Health (grants CA217065, CA217066, CA203101, CA159859, CA199376, NS097649-01, CA240953-01, NS096368, R01DK103901,R01AA027065, MH107367, N5105969, CA045726, CA050286, CA197718, CA154130, CA169117, CA171652, NS087913, NS089272), California Institute for Regenerative Medicine (CIRM, grants FA1-00607, DISC209649) and International Rett Syndrome Foundation.

Disclosures: Tariq Rana is a co-founder of, member of the scientific advisory board for, and has equity interest in ViRx Pharmaceuticals. Alysson Muotri is a co-founder and has equity interest in TISMOO, a company dedicated to genetic analysis focusing on therapeutic applications customized for autism spectrum disorder and other neurological disorders. David Cheresh is a co-founder of TargeGen and AlphaBeta Therapeutics, a new but currently unfunded company developing an antibody to integrin v5 involved in cancer treatment. The terms of these arrangements have been reviewed and approved by UC San Diego in accordance with its conflict of interest policies. In addition, Michael Diamond, of Washington University School of Medicine, is a consultant for Inbios and Atreca and serves on the Scientific Advisory Board of Moderna.

More:
Zika Virus' Key into Brain Cells ID'd, Leveraged to Block Infection and Kill Cancer Cells - UC San Diego Health

Koepka Tied for 3rd in Abu Dhabi in Return From Knee Injury – The New York Times

By Stem Cell Treatment

ABU DHABI, United Arab Emirates Brooks Koepka shot a 6-under 66 Thursday in his return to competition after a knee injury and was tied for third place after the opening round of the Abu Dhabi Championship.

Koepka, ranked No. 1 in the world, missed three months after re-injuring his knee when he slipped while walking off the tee on Oct. 18 at the CJ Cup in South Korea. He previously had stem cell treatment for a partially torn tendon in his patella.

The four-time major winner had physical therapy in San Diego for most of December and began to hit balls before Christmas. He has said he's pain free, but acknowledged earlier this week his left knee doesn't feel the same as my right.

Koepka is two shots behind co-leaders Shaun Norris, of South Africa, and Renato Paratore, of Italy.

He looked sharp Thursday, making birdies on two of the first three holes on the way to a bogey-free round.

The first day I picked up the club, same thing, felt like I hadn't left," Koepka said. I've done it for years and years. You don't forget how to swing the golf club.

It was a little sore last night, the American said, "just did some treatment on it, that's expected.

The 23-year-old Paratore is seeking his second European Tour title. He was beaten by Rasmus Hojgaard in a playoff at the Mauritius Open in December.

Koepka, who is tied with Australian Jason Scrivener, said his knee felt fine.

Sergio Garcia is among six players tied fourth after an opening 67.

Defending champion Shane Lowry opened with a 2-under 70.

___

View original post here:
Koepka Tied for 3rd in Abu Dhabi in Return From Knee Injury - The New York Times

Giraffe Will Go Through Risky Procedure At Cheyenne Mountain Zoo To Treat Ongoing Health Issues – CBS Denver

By Stem Cell Treatment

COLORADO SPRINGS, Colo. (CBS4) A 16-year-old giraffe named Mahali will go through a risky procedure as animal care specialists work to treat some ongoing health issues. Animal care specialists say Mahali has arthritis and fractures in his feet, which hes recently indicated have become painful.

Zoo officials say theyve treated similar conditions before with special shoes and stem cell injections but Mahali has recently regressed in his training and isnt allowing them to attempt those treatments.

Weve exhausted all of our usual treatment options. This means we are now gearing up for an anesthetization to immobilize and treat Mahali, officials stated Wednesday.

The VP of Mission and Programs, Dr. Liza, and Giraffe Animal Care Manager, Jason, explained that giraffe anesthesia is risky but say it is in Mahalis best interest in this case.

Read more:
Giraffe Will Go Through Risky Procedure At Cheyenne Mountain Zoo To Treat Ongoing Health Issues - CBS Denver

Novel form of cell-free therapy revealed by researchers – Drug Target Review

By Stem Cell Treatment

Researchers have developed cytochalasin B-induced membrane vesicles which they suggest could be a new form of cell-free therapy in regenerative medicine.

Work on extracellular microvesicles (ECMVs) derived from human mesenchymal stem cells (MSCs) has revealed a potential new form of cell-free therapy.

ECMVs are microstructures surrounded by a cytoplasm membrane; they have proven to be a prospective therapeutic tool in regenerative medicine due to their biocompatibility, miniature size, safety and regenerative properties. These can be used to circumvent the limitations of existing cell therapies without losing any effectiveness.

Cell therapies are grafts or implants of living tissue, such as bone marrow transplants, used to replace and regenerate damaged organ tissue. They currently have limited applications, as they work differently dependent on conditions and the environment they are placed into. They can also be rejected by the immune system.

A study at Kazan Federal University, Russia, has investigated cytochalasin B-induced membrane vesicles (CIMVs) which are also derived from MSCs and are very similar to natural ECMVs.

Proteome analysis of human MSCs and CIMVs-MSCs. Venn diagram of identified proteins MSCs and CIMVs-MSCs (A). Distribution of the identified proteins in organelles, percent of unique identified proteins (B) (credit: Kazan Federal University).

The scientists studied and characterised the biological activity of MSC-derived CIMVs. A number of biologically active molecules were found in CIMVs, such as growth factors, cytokines and chemokines; their immunophenotype was also classified.They also found that CIMVs could stimulate angiogenesis in the same way as stem cells.

The team came to the conclusion that human CIMVs-MSCs can be used for cell-free therapy of degenerative diseases. Induction of therapeutic angiogenesis is necessary for the treatment of ischemic tissue damage (eg, ischemic heart disease, hind limb ischemia, diabetic angiopathies and trophic ulcers) and neurodegenerative diseases (eg, multiple sclerosis and Alzheimers disease), as well as therapies for damage of peripheral nerves and spinal cord injury.

The group say they are continuing to research the therapeutic potential for artificial microvesicles for autoimmune diseases.

The study was published in Cells.

Continue reading here:
Novel form of cell-free therapy revealed by researchers - Drug Target Review

Choosing the Best Therapy for Patients with Chronic Lymphocytic Leukemia – Curetoday.com

By Stem Cell Treatment

With many targeted treatment options for patients with CLL to use upfront, the question arises as to which one is best for the individual.

Targeted therapies, such as Imbruvica (ibrutinib), Calquence (acalabrutinib) and Venclexta (venetoclax) plus Gazyva (obinutuzumab), have been approved by the Food and Drug Administration (FDA) and have shown to keep patients in remission or reduce the risk of disease progression or death.

The most recent study is the ELEVATE-TN study, which led to the approval of acalabrutinib, Woyach, an associate professor at The Ohio State University Comprehensive Cancer CenterJames, said in an interview with OncLive, a sister publication of CURE. That study was (Leukeran [chlorambucil])/obinutuzumab versus acalabrutinib alone versus acalabrutinib plus obinutuzumab. Acalabrutinib and acalabrutinib/obinutuzumab had significantly improved (progression free survival [PFS]) with about a 90% two-year PFS rate.

In addition to using these medications alone, researchers are studying their use in combination with other drugs, such as Venclexta with Imbruvica, a type of Brutons tyrosine kinase (BTK) inhibitor. BTK inhibitors work by keeping the cancer cells from growing and have shown great results in CLL.

One study looked at combining venetoclax with the BTK inhibitor (Imbruvica) to see if you can both capitalize on the efficacy of the two agents, and then potentially get patients into such deep remissions that they can come off therapy, she said. At the 2019 ASH Annual Meeting, we had the follow-up of The University of Texas MD Anderson Cancer Center study in both the frontline and relapsed/refractory settings, in which the majority of patients are getting minimal residual disease-negative responses. There are a lot of complete responses with fairly limited follow-up off treatment. Most patients are still in remission.

Side effect profile and patient preference can be used to help guide oncologists on which treatment is best to start with, Woyach explained. We have the discussion for patients who are very high-risk, meaning those with TP53 mutations or 17p deletions, she said. The data with the BTK inhibitors looks a little bit stronger compared with that fixed duration of venetoclax/obinutuzumab. For those patients, I'm still trying to steer them towards the BTK inhibitor; however, it's not wrong to (give) venetoclax/obinutuzumab to those patients either.

Imbruvica has the stronger safety and efficacy data, Woyach added. However, with longer follow-up, Imbruvica has more side effects, such as hypertension; bleeding risk; and atrial fibrillation (AFib), or an irregular heartbeat, which has been seen in 10% to 15% of patients, generally those who are older. In addition, arthralgia, myalgia, diarrhea, bruising and gastrointestinal issues can also been experience by patients treated with Imbruvica.

Although patients have to take Calquence twice a day, the medication has fewer side effects, including less cases of AFib and hypertension. The same bleeding risk as Imbruvica is present, Woyach said. She added that the downside to the Venclexta and Gazyva combination is that they are time consuming.

Overall, these therapies continue to show great promise, but if a patient relapses or becomes resistant to therapy, Woyach explained that reversible BTK inhibitors are in development. A few of those reversible molecules (were presented) at the 2019 ASH Annual Meeting and showed very interesting efficacy; these included ARQ 531 and LOXO-305, she said.

This article was adapted from an article that originally appeared on OncLive, titled Woyach Highlights Progress and Next Steps in CLL Paradigm.

Read the original post:
Choosing the Best Therapy for Patients with Chronic Lymphocytic Leukemia - Curetoday.com

Astellas, Adaptimmune to develop CAR-T & TCR T-cell therapies – BSA bureau

By Stem Cell Treatment

Astellas will pay Adaptimmune an upfront payment, research funding, development and commercial milestones, and royalties on net sales on co-commercialized products

Japan based Astellas Pharma Inc., through its wholly-owned subsidiary Universal Cells, Inc. and Adaptimmune Therapeutics plc, a leader in cell therapy to treat cancer, have announced that they have entered into a co-development and co-commercialization agreement to bring new stem-cell derived allogeneic T-cell therapies to people with cancer.

Astellas and Adaptimmune will agree on up to three targets and co-develop T-cell therapy candidates directed to those targets. These targets will exclude target specific T-cell products in pre-clinical or clinical trials or those developed for other partners at Adaptimmune. The collaboration will leverage Adaptimmune's target identification and validation capabilities for generating target-specific T-cell Receptors (TCRs), chimeric antigen receptors (CARs), and HLA-independent TCRs that recognize surface epitopes independently of the HLA profile of the tumor cell. The collaboration will also utilize Astellas Universal Donor Cell and Gene Editing Platform it obtained through the acquisition of Seattle-based Universal Cells.

Adaptimmune has been collaborating with Universal Cells since 2015 on development of gene-edited iPSC cell lines, for which Adaptimmune has rights to develop and commercialize resulting T-cell therapy products using its proprietary process for generating T cells from stem cells without the use of feeder cell lines.

Astellas will fund research up until completion of a Phase 1 trial for each candidate. Upon completion of the Phase 1 trial for each candidate, Astellas and Adaptimmune will elect whether to progress with co-development and co-commercialization of the candidate, or to allow the other Party to pursue the candidate independently through a milestone and royalty bearing licence, with the agreement allowing for either company to opt out. The companies will each have a co-exclusive licence covering the co-development and co-commercialization of the product candidates within the field of T-cell therapy. If a candidate is developed by one company only, the appropriate licences will become exclusive to the continuing party.

Astellas will also have the right to select two targets and develop allogeneic cell therapy candidates independently. Astellas will have sole rights to develop and commercialize these products, subject to necessary licenses and the payment of milestones and royalties.

Under the terms of the agreement, Adaptimmune may receive up to $897.5 million in payments, including:

In addition, Adaptimmune will receive research funding of up to $7.5 million per year.

Finally, Adaptimmune would receive tiered royalties on net sales in the mid-single to mid-teen digits.

Under the terms of the agreement, Astellas may receive up to $552.5 million, including:

In addition, Astellas would receive tiered royalties on net sales in the mid-single to mid-teen digits.

To the extent that Astellas and Adaptimmune co-develop and co-commercialize any T-cell therapy, they will equally share the costs of such co-development and co-commercialization, with the resulting profits from co-commercialization also shared equally. Further details governing co-development and co-commercialization will be articulated in a product-specific commercialization agreement.

The impact of this transaction on Astellas financial results in the fiscal year ending March 31, 2020 will be limited.

Continued here:
Astellas, Adaptimmune to develop CAR-T & TCR T-cell therapies - BSA bureau

Melton parents of seriously ill little girl appeal for help to treat her – Melton Times

By Stem Cell Treatment

The parents of a two-year-old Melton girl, who suffers regular seizures and has brain damage, are desperately trying to raise tens of thousands of pounds to pay for treatment here and abroad to help her live a healthier life.

Anika Wojciechowski has been diagnosed with Wolf-Hirschhorn syndrome and has spent a large part of her short life being treated in hospital.

She has severe epilepsy, endures up to 90 seizures a day and often requires oxygen or CPR to revive her.

Dad, Mariusz, and mum, Katarzyna, are hopeful that treatment elsewhere in Europe can ease their daughters condition depite being told by doctors in the UK that there is little more they can do for her other than prescribing the medication she is on.

They are hopeful that a course of growth hormone therapy and, possibly, stem cell transplantation can help her.

Mariusz told the Melton Times: Anika needs to be watched 24/7 as nobody knows what the next seizure is going to be like.

Her seizures are unpredictable and so one time she will need a bit of oxygen to get over it but the next time she will have a cardiac or respiratory arrest and need CPR done before an ambulance arrives.

He added: Every day, Anika proves how brave she is and she doesnt give up despite everything that has happened to her.

Last year she spent three months in intensive care, being incubated many times and having continuous doses of morphine, ketamine and many other medical agents which kept her in a pharmacological coma to stop her continuous epilepsy attacks.

Many doctors have already given up and see no hope for her but we do continue to fight for her to get the treatment abroad which can help her.

Anika spent the first month of her life in hospital after being born at just 34 weeks and weighing only just over three pounds.

But she developed severe epilepsy and was then diagnosed with the rare Wolf-Hirschhorn syndrome, where the symptoms are a characteristic facial appearance, delayed growth and development, intellectual disability and seizures.

Last year, she was also found to have brain damage and lost her eyesight, all speech abilities and the power in her legs and hands.

In addition, she is very delicate and easily catches a cold and infections, which also result in hospital stays.

Medical professionals did not give her any chance of survival but the couple have sought advice and they say recent initial treatment in europe has perked her up.

Anika already feels and looks better, said Mariusz

She has begun to smile and, even wonderfully, laugh.

Her fragile body is getting stronger and Anika is able to partially control the movement of her head and hands.

What has brought such a great positive effect is only the beginning of the whole treatment, which unfortunately is expensive and requires travelling abroad.

Mariusz and Katarzyna have used their savings and a large proportion of their earnings to fund treatment for their daughter.

They are also grateful for the 4,000 people have pledged on online fundraising pages and collection boxes in local shops.

The couple plan to visit clinics in Poland, Italy and Germany to seek treatment and their main aim is to fund growth hormone therapy for Anika, which is not available on the NHS and which costs around 10,000 just to get started on.

Mariusz added: We are asking people to please help Anika because we know that she can have a normal life and enjoy it like other children but time is running out.

Go to http://www.facebook.com/marian.wojciech.9 to pledge money for Anikas treatment.

See the rest here:
Melton parents of seriously ill little girl appeal for help to treat her - Melton Times

→←