Monthly Archives: May 2020

UWMadison announces its fourth round of cluster hires – University of Wisconsin-Madison

Posted: May 7, 2020 at 7:46 pm

Artificial intelligence, ethics in technology, the origins of life, astrophysical data these exciting but complex subjects are the focus of the University of WisconsinMadisons fourth round of cluster hires, the Office of the Provost announced today.

The hires, which are made as a group across departments rather than individually within departments, build upon the universitys existing strengths. They foster collaborative research, education and outreach by creating new interdisciplinary areas of knowledge.

UWMadison first launched the Cluster Hiring Initiative in 1998 as an innovative partnership between the university, state and the Wisconsin Alumni Research Foundation. In its first phase, the initiative authorized nearly 50 clusters, adding nearly 150 new faculty members through several rounds of hiring. In 2017, the Office of the Provost authorized phase two of the initiative, with a goal of supporting at least 12 clusters.

Previous clusters were announced in April 2019 andSeptemberandFebruaryof 2018. This latest round brings the total of clusters supported to 19. In light of the COVID-19 pandemic, however, each cluster will be given at least two years to complete its hiring plans. New cluster competition will be suspended for at least the next academic year.

The latest cluster hires are:

Artificial Intelligence in Precision Medical Imaging and Diagnostics

Proposal advanced by: Thomas Grist, professor of radiology, medical physics and biomedical engineering; Kristin Eschenfelder, associate director of the School of Computing, Data and Information Sciences; Rob Nowak, professor of electrical and computer engineering, computer sciences, statistics and biomedical engineering; Vallabh Sambamurthy, dean of the Wisconsin School of Business.

Through new approaches to data acquisition and analysis, advances in artificial intelligence are poised to revolutionize the way in which medical imaging affects clinical care and scientific discoveries in medicine. This cluster outlines three key faculty positions that will be foundational to an expansion of UWMadisons leadership in the field. It will also address urgent opportunities for curriculum development in areas of interest to multiple colleges and schools on campus and extramural entities.

Next-generation medical imaging uses AI techniques to improve its diagnostic accuracy and predictive power, enabling advances in basic understanding of human disease, treatment monitoring and long-term surveillance of disease.

Collaborations like those forged by the cluster hire will contribute to the realization of the full potential of AI for precision medical imaging and diagnostics.

Ethics in Computing, Data, and Information

Proposal advanced by: Alan Rubel, professor in the Information School and director of the Center for Law, Society and Justice; Michael Titelbaum, Vilas Distinguished Achievement Professor and Chair of the Department of Philosophy; Loris DAntoni, professor of computer sciences; Aws Albarghouthi, professor of computer sciences; Noah Weeth Feinstein, director of the Holtz Center for Science, Technology and Society and a professor of curriculum and instruction and community and environmental sociology.

Computational systems, data analytics, artificial intelligence and algorithmic decision systems affect large and important facets of society, including governance, education, commerce, democracy and media. These tools can be used to advance social goods, but they can also go awry, used for bad purposes by bad actors. The tools can also reflect and engender unfair social structures.

To effectively address ethical issues in AI, data, and information systems requires collaboration between scholars working on computational systems, on the social facets of information technologies, and on conceptual and moral questions about how such systems function and how they are used.

UWMadison is well-positioned to be a world leader in these areas because of its current strengths and existing collaborations. The cluster proposes hiring three faculty members working on distinct facets of the ethics of computing, data and information.

Exploring the Origins of Life Across the Galaxy

Proposal advanced by: Sebastian Heinz, professor and chair of astronomy; David Baum, professor of botany; Judith Burstyn, professor and chair of chemistry; Greg Tripoli, professor and chair of atmospheric and oceanic sciences; Jeff Hardin, professor and chair of integrative biology; Ken Cameron, professor and chair of botany; Chuck DeMets, professor and chair of geoscience; Annie Bauer, assistant professor of geoscience; Tristan LEcuyer, professor of atmospheric and oceanic sciences; Robert Mathieu, professor of astronomy; Steve Meyers, professor of geoscience; Phillip Newmark, professor of integrative biology; Andrew Vanderburg, assistant professor of astronomy; Susanna Widicus Weaver, professor of chemistry; John Yin, professor of chemical and biological engineering; Tehshik Yoon, professor of chemistry; Ke Zhang, assistant professor of astronomy.

Questions about the origins and nature of life are as old as humanity itself. Today, the search for understanding the origin of life extends to the cosmos, as recent work has uncovered countless planets orbiting stars throughout the Milky Way, each potentially bearing life of its own. But how do we detect life on planets we can never visit? And how do we know how common life might be if we dont know how it arose on Earth?

The search for evidence of life on other planets is by nature interdisciplinary. Chemistry, biology and geoscience combine to understand how life arose on our planet and how it might have done so on other worlds, while astronomy and atmospheric sciences can probe for evidence of that life from light-years away. This cluster will allow the hiring of researchers who straddle these fields and who can bridge the gaps between expertise across the participating departments. The group will also establish the Wisconsin Center for Origins Research to house new and existing faculty and encourage new collaborations in astrobiology.

Breakthrough Science with Multi-messenger Astrophysical Data

Proposal advanced by: Albrecht Karle, professor of physics; Keith Bechtol, assistant professor of physics; Francis Halzen, professor of physics; Kael Hanson, professor of physics; Sebastian Heinz, professor and chair of astronomy; Sebastian Raschka, assistant professor of statistics; Justin Vandenbroucke, associate professor of physics; Jun Zhu, professor and chair of statistics; Ellen Zweibel, professor of astronomy.

For millennia, humans learned about the night sky only from the light from distant stars. But recently, astrophysicists have gained access to signals that go beyond light. These messengers about the universe include gravitational waves and neutrinos ghostly particles that rarely interact with other matter. UWMadison is the headquarters of the worlds largest neutrino observatory, IceCube, which surveys a billion tons of Antarctic ice for signs of rare neutrino collisions.

Now, the IceCube project is preparing for a major upgrade to generation two. This cluster hire will invest in the astronomy, physics and statistics faculty necessary to continue and expand UWMadisons leadership in multi-messenger astrophysics. This data-heavy field requires collaborations between these three fields to probe the constant stream of information recorded by IceCube and to find the sources of the neutrinos that stream toward Earth. That analysis can help answer fundamental questions about the physical laws governing the universe and help us understand complex phenomena like black holes and cosmic rays.

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What Do New Neurons in the Brains of Adults Actually Do? – The Scientist

Posted: May 7, 2020 at 7:44 pm

In the spring of 2019, neuroscientist Heather Cameron set up a simple experiment. She and her colleagues put an adult rat in the middle of a plastic box with a water bottle at one end. They waited until the rat started drinking and then made a startling noise to see how the animal would respond. The team did this repeatedly with regular rats and with animals that were genetically altered so that they couldnt make new neurons in their hippocampuses, a brain region involved in learning and memory. When the animals heard the noise, those that could make new hippocampal neurons immediately stopped slurping water and looked around, but the animals lacking hippocampal neurogenesis kept drinking. When the team ran the experiment without the water bottle, both sets of rats looked around right away to figure out where the sound was coming from. Rats that couldnt make new neurons seemed to have trouble shifting their attention from one task to another, the researchers concluded.

Aging humans, in whom neurogenesis is thought to decline, often have trouble remembering details that distinguish similar experiences.

Its a very surprising result, says Cameron, who works at the National Institute of Mental Health (NIMH) in Bethesda, Maryland. Researchers studying neurogenesis in the adult hippocampus typically conduct experiments in which animals have had extensive training in a task, such as in a water maze, or have experienced repetitive foot shocks, she explains. In her experiments, the rats were just drinking water. It seemed like there would be no reason that the hippocampus should have any role, she says. Yet in animals engineered to lack hippocampal neurogenesis, the effects are pretty big.

The study joins a growing body of work that challenges the decades-old notion that the primary role of new neurons within the adult hippocampus is in learning and memory. More recently, experiments have tied neurogenesis to forgetting, one possible way to ensure the brain doesnt become overloaded with information it doesnt need, and to anxiety, depression, stress, and, as Camerons work suggests, attention. Now, neuro-scientists are rethinking the role that new neurons, and the hippocampus as a whole, play in the brain.

Most of the research into neurogenesis involves boosting or inhibiting animals generation of new neurons, then training animals on a complex memory task such as finding a treat in a maze, and later retesting the animals. Decreasing neurogenesis tends to hamper the animals ability to remember.

Alzheimers disease, Parkinsons disease

Training mice or rats on a memory task before manipulating neurogenesis has also been found to affect the strength of the trained memory. Boosting neurogenesis reduced the memorys strength, perhaps an extreme form of forgetting that at normal levels avoids the remembering of unnecessary details.

Alzheimers disease and other forms of dementia

Research has linked decreased neurogenesis with more anxious and depressive behaviors in mice. Stress can reduce neurogenesis, ultimately leading mice to be more anxious in future stressful situations.

PTSD, anxiety, depression

Research has linked decreased neurogenesis with trouble switching focus.

Autism

The first hint that adult animal brains may make new neurons appeared in the early 1960s, when MIT neurobiologist Joseph Altman used radioactive labeling to track the proliferation of nerve cells in adult rats brains.Other data published in the 1970s and 1980s supported the conclusion, and in the 1990s, Fred Rusty Gage and his colleagues at the Salk Institute in La Jolla, California, used an artificial nucleotide called bromodeoxyuridine (BrdU) to tag new neurons born in the brains of adult rats and humans. Around the same time, Elizabeth Gould of Princeton University and her collaborators showed that adult marmoset monkeys made new neurons in their hippocampuses, specifically in an area called the dentate gyrus. While some researchers questioned the strength of the evidence supporting the existence of adult neurogenesis, most of the field began to shift from studying whether adult animal brains make new neurons to what role those cells might play.

In 2011, Ren Hen at Columbia University and colleagues created a line of transgenic mice in which neurons generated by neuro-genesis survived longer than in wildtype mice. This boosted the overall numbers of new neurons in the animals brains. The team then tested the modified mices cognitive abilities. Boostingnumbers of newly born neurons didnt improve the mices performances in water mazes or avoidance tasks compared with control mice. But it did seem to help them distinguish between two events that were extremely similar. Mice with more new neurons didnt freeze as long as normal mice when put into a box that was similar to but not exactly the same as one in which theyd experienced a foot shock in earlier training runs.

These results dovetailed with others coming out at the time, particularly those showing that aging humans, in whom neurogenesis is thought to decline, often have trouble remembering details that distinguish similar experiences, what researchers call pattern separation. The line of thinking is that the memories that are most likely to be impacted by neurogenesis are memories that are really similar to each other, says Sarah Parylak, a staff scientist in Gages lab at the Salk Institute.

As insights into pattern separation emerged, scientists were beginning to track the integration of new rodent neurons into existing neural networks. This research showed that new neurons born in the dentate gyrus had to compete with mature neurons for connections to neurons in the entorhinal cortex (EC), a region of the brain with widespread neural networks that play roles in memory, navigation, and the perception of time. (See Memories of Time on page 32.) Based on detailed anatomical images, new dentate gyrus neurons in rodents appeared to tap into preexisting synapses between dentate gyrus neurons and EC neurons before creating their own links to EC neurons.

To continue exploring the relationship between old and new neurons, a group led by the Harvard Stem Cell Institutes Amar Sahay, who had worked with Hen on the teams 2011 study, wiped out synapses in the dentate gyruses of mice. The researchers overexpressed the cell deathinducing protein Krppel-like factor 9 in young adult, middle-aged, and old mice to destroy neuronal dendritic spines, tiny protrusions that link up to protrusions of other neurons, in the brain region. Those lost connections led to increased integration of newly made neurons, especially in the two older groups, which outperformed age-matched, untreated mice in pattern-separation tasks. Adult-born dentate gyrus neurons decrease the likelihood of reactivation of those old neurons, Sahay and colleagues concluded, preventing the memories from being confused.

Parylak compares this situation to going to the same restaurant after it has changed ownership. In her neighborhood in San Diego, theres one location where shes dined a few times when the restaurant was serving different cuisine. Its the same location, and the building retains many of the same features, so the experiences would be easy to mix up, she says, but she can tell them apart, possibly because of neurogenesiss role in pattern separation. This might even hold true for going to the same restaurant on different occasions, even if it served the same food.

Thats still speculative at this point. Researchers havent been able to watch neurogenesis in action in a living human brain, and its not at all clear if the same thing is going on there as in the mouse brains they have observed. While many scientists now agree that neurogenesis does occur in adult human brains, there is little consensus about what it actually does. In addition to the work supporting a role for new neurons in pattern separation, researchers have accumulated evidence that it may be more important for forgetting than it is for remembering.

In recent years, images and videos taken with state-of-the-art microscopy techniques have shown that new neurons in the dentate gyrus of the hippocampus go through a series of changes as they link up to existing networks in the brain.

A neural stem cell divides to generate a new neuron (green).

As the new neuron grows, it rotates from a horizontal to a vertical position and connects to an interneuron (yellow) in a space called the hilus that sits within the curve of the dentate gyrus. The young neuron also starts making connections with well-established dentate gyrus neurons (blue) as well as neurons in the hippocampus (red).

Once connections are formed, mature neurons send signals into the new neuron, and the cell starts firing off more of its own signals. At around four weeks of age, the adult-born neuron gets hyperexcited, sending electrical signals much more often than its well-established neuronal neighbors do.

As the new neuron connects with still more neurons, interneurons in the hilus start to send it signals to tamp down its activity.

It seems counterintuitive for neurogenesis to play a role in both remembering and forgetting, but work by Paul Frankland of the Hospital for Sick Children Research Institute in Toronto suggests it is possible. In 2014, his team showed that when mice made more new neurons than normal, they were more forgetful. He and his colleagues had mice run on wheels to boost levels of neurogenesis, then trained the animals on a learning task. As expected, they did better than control mice who hadnt exercised. (See How Exercise Reprograms the Brain, The Scientist, October 2018.) In other animals, the researchers boosted neurogenesis after the mice learned information thought to be stored, at least in the short term, in the hippocampus. When we did that, what we found was quite surprising, Frankland says. We found a big reduction in memory strength.

His team was puzzled by the result. Adding to the confusion, the researchers had observed a larger effect in memory impairment with mice that learned, then exercised, than they had seen in memory improvement when the mice ran first and then learned. As he dug into the literature, Frankland realized the effect was what other neuroscientists had called forgetting. He found many theoretical papers based on computational modeling that argued that as new neurons integrate into a circuit, the patterns of connections in the circuit change, and if information is stored in those patterns of connections, that information may be lost. (See Memory Munchers on page 21.)

The notion surprised other neuroscientists, mainly because up to that point theyd had two assumptions related to neurogenesis and forgetting. The first was that generating new neurons in a normal animal should be good for memory. The second was that forgetting was bad. The first assumption is still true, Frankland says, but the second is not. Many people think of forgetting as some sort of failure in our memory systems, he explains. Yet in healthy brains theres tons of forgetting happening all of the time. And, in fact, its important for memory function, Frankland says. It would actually be disadvantageous to remember everything we do.

Experiments have tied neurogenesis to forgetting, anxiety, depression, stress, and attention.

Parylak says this idea of forgetting certainly has provoked a lot of discussion. Its unclear, for example, whether the mice in Franklands experiments are forgetting, or if they are identifying a repeat event as something novel. This is the point, she explains, where doing neurogenesis research in humans would be beneficial. You could ask a person if theyd actually forgotten or if they are making some kind of extreme discrimination.

Despite the questions regarding the results, Frankland and his colleagues continued their work, testing mices forgetfulness with all types of memories, and more recently they asked whether the forgetting effect jeopardized old and new memories alike. In experiments, his team gave mice a foot shock, then boosted hippocampal neurogenesis (with exercise or a genetic tweak to neural progenitor cells), and put the mice in the same container theyd been shocked in. With another group of mice, the researchers waited nearly a month after the foot shock before boosting neurogenesis and putting the mice back in the container. Boosting the number of new neurons, the team found, only weakened the newly made memory, but not one that had been around for a while. This makes a lot of sense, Frankland says. As our memories of everyday events gradually get consolidated, they become less and less dependent on the hippocampus, and more dependent on another brain region: the cortex. This suggests that remote memories are less sensitive to changes in hippocampal neurogenesis levels.

The hippocampus tracks whats happened to you, Frankland says. Much of thats forgotten because much of it is inconsequential. But every now and then something interesting seems to happen, and its these eventful memories that seem to get backed up in other areas of the brain.

Researchers think neurogenesis helps the brain distinguish between two very similar objects or events, a phenomenon called pattern separation. According to one hypothesis, new neurons excitability in response to novel objects diminishes the response of established neurons in the dentate gyrus to incoming stimuli, helping to create a separate circuit for the new, but similar, memory.

At NIMH, one of Camerons first studies looking at the effects of neurogenesis tested the relationship between new neuronal growth and stress. She uncovered the connection studying mice that couldnt make new neurons and recording how they behaved in an open environment with food at the center. Just like mice that could still make new neurons, the neuro-genesis-deficient mice were hesitant to go get the food in the open space, but eventually they did. However, when the animals that couldnt make new neurons were stressed before being put into the open space, they were extremely cautious and anxious, whereas normal mice didnt behave any differently when stressed.

Cameron realized that the generation of new neurons also plays a role in the brain separate from the learning and memory functions for which there was growing evidence. In her experiments, we were looking for memory effects and looked for quite a while without finding anything and then stumbled onto this stress effect, she says.

The cells in the hippocampus are densely packed with receptors for stress hormones. One type of hormone in particular, glucocorticoids, is thought to inhibit neurogenesis, and decreased neurogenesis has been associated with depression and anxiety behaviors in rodents. But there wasnt a direct link between the experience of stress and the development of these behaviors. So Cameron and her colleagues set up an experiment to test the connection.

When the team blocked neurogenesis in adult mice and then restrained the animals to moderately stress them, their elevated glucocorticoid levels were slow to recover compared with mice that had normal neurogenesis. The stressed mice that could not generate new neurons also acted oddly in behavioral tests: they avoided food when put in a new environment, became immobile and increasingly distressed when forced to swim, and drank less sugary water than normal mice when it was offered to them, suggesting they dont work as hard as normal mice to experience pleasure. Impaired adult neurogenesis, the experiments showed, played a direct role in developing symptoms of depression, Cameron says.

The notion that neurogenesis and stress might be tied directly to our mental states led Cameron to look back into the literature, where she found many suggestions that the hippocampus plays a role in emotion, in addition to learning and memory. Even Altman, who unexpectedly identified neurogenesis in adult rodents in the 1960s, and colleagues suggested as much in the 1970s. Yet the argument has only appeared sporadically in the literature since then. Stress is complicated, Cameron says; its hard to know exactly how stressful experiences affect neurogenesis or how the generation of new neurons will influence an animals response to stress. Some types of stress can decrease neurogenesis while others, such as certain forms of intermittent stress, can increase new neuronal growth. Last year, Cameron and colleagues found that generating new neurons helps rats used to model post-traumatic stress disorder recover from acute and prolonged periods of stress.

Neurogenesis appears to play a role in both remembering and forgetting.

Her work has also linked neurogenesis to other characteristics of rodent behavior, including attention and sociability. In 2016, with Gould at Princeton and a few other collaborators, she published work suggesting that new neurons are indeed tied to social behavior. The team created a hierarchy among rats, and then deconstructed those social ranks by removing the dominant male. When the researchers sacrificed the animals and counted new neurons in their brains, the rats from deconstructed hierarchies had fewer new neurons than those from control cages with stable ranks. Rats with uncertain hierarchies and fewer new neurons didnt show any signs of anxiety or reduced cognition, but they werent as inclined as control animals to spend time with new rats put into their quarters, preferring to stick with the animals they knew. When given a drugoxytocinto boost neurogenesis, they once again began exploring and spending time with new rats that entered their cages.

The study from Camerons lab on rats ability to shift their attention grew out of the researchers work on stress, in which they observed that rodents sometimes couldnt switch from one task to the next. Turning again to the literature, Cameron found a study from 1969 that seemed to suggest that neurogenesis might affect this task-switching behavior. Her team set up the water bottle experiments to see how well rats shifted attention. Inhibiting neurogenesis in the adult mice led to a 50 percent decrease in their ability to switch their focus from drinking to searching for the source of the sound.

This paper is very interesting, says J. Tiago Gonalves, a neuroscientist at Albert Einstein College of Medicine in New York who studies neurogenesis but was not involved in the study. It could explain the findings seen in some behavioral tasks and the incongruences between findings from different behavioral tasks, he writes in an email to The Scientist. Of course, follow-up work is needed, he adds.

Cameron argues that shifting attention may be yet another behavior in which the hippocampus plays an essential role but that researchers have been overlooking. And there may be an unexplored link between making new neurons and autism or other attention disorders, she says. Children with autism often have trouble shifting their attention from one image to the next in behavioral tests unless the original image is removed.

Its becoming clear, Cameron continues, that neurogenesis has many functions in the adult brain, some that are very distinct from learning and memory. In tasks requiring attention, though, there is a tie to memory, she notes. If youre not paying attention to things, you will not remember them.

Many, though not all, neuroscientists agree that theres ongoing neurogenesis in the hippocampus of most mammals, including humans. In rodents and many other animals, neurogenesis has also been observed in the olfactory bulbs. Whether newly generated neurons show up anywhere else in the brain is more controversial.

There had been hints of new neurons showing up in the striatum of primates in the early 2000s. In 2005,Heather Cameronof the National Institute of Mental Health and colleagues corroborated those findings, showing evidence of newly made neurons in therat neocortex, a region of the brain involved in spatial reasoning, language, movement, and cognition, and in the striatum, a region of the brain involved in planning movements and reacting to rewards, as well as self-control and flexible thinking (J Cell Biol, 168:41527). Nearly a decade later, using nuclear-bomb-test-derivedcarbon-14 isotopesto identify when nerve cells were born,Jonas Frisnof the Karolinska Institute in Stockholm and colleagues examined the brains of postmortem adult humans and confirmed thatnew neurons existed in the striatum(Cell, 156:107283, 2014).

Those results are great, Cameron says. They support her idea that there are different types of neurons being born in the brain throughout life. The problem is theyre very small cells, theyre very scattered, and therere very few of them. So theyre very tough to see and very tough to study.

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South Sound Community Bands Together To Save Local Lives – southsoundtalk.com

Posted: May 7, 2020 at 7:43 pm

Submitted by Bloodworks Northwest

In the spirit of perseverance, sports teams Tacoma Rainiers, Tacoma Defiance, and OL Reign will host a Pop-Up Donor Center experience at their home field Cheney Stadium and ClubCorp will host a Pop-Up Donor Center at Canterwood Golf & Country Club. Additionally, Metro Parks Tacoma will provide support as both Pop-Ups combine to make the South Sound Pop-Up Donor Center from Monday, May 4 to Saturday, May 16, 2020.

The two Pop-Up blood donationlocations provide key areas for community members to give blood in the SouthSound. With COVID-19 social distancing recommendations, traditional blooddrives and bloodmobiles are temporarily unavailable further limitingopportunities to give blood. Bloodworks has turned to an innovative alternativewith Pop-Up Centers that are held in large venues, allowing higher level ofspace and safety for donors and staff. With current limitations to usage,Cheney Stadium and Canterwood Golf & Country Club will be utilized toprovide much needed support to the health and wellbeing of the South Soundcommunity.

Were thrilled to be partneringwith the South Sound sports community to ensure the local blood supply is readyto respond to the increased need for blood as hospitals prepare to resumeelective surgeries, said Bloodworks Northwest President & CEO Curt Bailey.The health of our community depends on donors making blood donation a regularhabit. Creating this opportunity for people to donate blood at Cheney Stadiumand Canterwood Golf & Country Club during this crucial time will help keepour community safe.

We R Tacoma is committed tosupporting the entire Puget Sound region, and during these difficult times areproud to provide Bloodworks NW our space in their efforts to mitigate theshortage of available blood in our region, said Tacoma Rainiers AssistantGeneral Manager Nick Cherniske. We hope the use of Cheney Stadium encouragesgreat participation as we come together for the greater community needs.

One of the many ways theSouth Sound community has been impacted by the COVID-19 crisis is the risk tothe supply of blood to Tacoma area hospitals, said Bill Predmore, CEO ofOL Reign. Bloodworks Northwest is doing tremendous work to address thischallenge. We are proud to support Bloodworks Northwest on this importantinitiative and encourage all supporters of OL Reign to donate if they are ableto do so.

People of all blood types are stillneeded every day to make an appointmentto give blood in support of cancer patients, trauma victims, premature babies, or totreat severely ill COVID-19 patients, among others. The unified effortby the teams, venues and organizations come at a crucial point when hospitalsproject the possibility of resuming elective surgeries. The increase in theneed for blood calls for an increase in donors to ensure a safe and stableblood supply.

Being involved in our community isa cornerstone of our mission at Canterwood Golf & Country Club, saidCanterwoood Golf & Country Club General Manager Tyler Hathaway. We aretruly grateful to have the opportunity to partner with Bloodworks to make sucha positive impact in so many lives during this very unique and uncertain time.

Many of us are looking fortangible ways we can help those whose lives are being upended on many frontsright now, said Shon Sylvia, Executive Director of Metro Parks Tacoma. Ifyoure in good health, we ask you to support the vital work of our partners atBloodworks by donating blood during this critical time of need.

Donors are urged to make theirone-hour donation appointmenttoday as a safe and essential action to support local patients. In accordancewith current social distancing guidelines, only scheduled appointments will beallowed and no walk-ins, guests, or people under age 16 are permitted onsite.On the day of their appointment, donors are invited to wear team gear as theysave a life and spread the word with #SouthSoundProud.

Also supporting the effort are 7Seas Brewing, Tims Cascade Snacks, Pepsi, and Sees Candies, which areproviding extra refreshments and perks for all donors at the South Sound Pop-UpDonor Center.

Bloodworks has posted informationaddressing questions and concerns for blood donors at bloodworksnw.org/coronavirus.Blood donation takes about an hour from registration to post-donationrefreshment. Information about who can donate andwhere, is available at http://www.bloodworksnw.org.

Canterwood Golf & Country Club Clubhouse 12606 54th Avenue NW Gig Harbor, WA 98332

Cheney Stadium Suites 2502 S Tyler St. Tacoma, WA 98405

May 4 May 16, 2020 Possibility of extension through the end of May

Sign-Up Link: https://schedule.bloodworksnw.org/DonorPortal/GroupLanding.aspx?s=494B

By appointment only

For the latest information on COVID-19 please visit theCDC website and Washington State Department of Health COVID-19 main page.

Appointments and information at BloodworksNW.org,800-398-7888, or text bloodapp to 91985 to receive a link on your phone. Pleasecheck website forextended donor center hours.

About Bloodworks Northwest Bloodworks Northwest isbacked by 75 years of Northwest history and 250,000 donors. It is local,nonprofit, independent, volunteer-supported and community-based. A recognizedleader in transfusion medicine, Bloodworks serves patients at hospitals in Washington,Oregon and Alaska partnering closely with local hospitals to deliver thehighest level of patient care. Comprehensive services include blood components,complex cross-matching, specialized lab services for organ transplants, carefor patients with blood disorders, and collection of cord blood stem cells forcancer treatment. Bloodworks Research Institute performs leading-edge researchin blood biology, transfusion medicine, blood storage and treatment of blooddisorders. Patients with traumatic injuries, undergoing surgeries or organtransplantation, or receiving treatment for cancer and blood disorders alldepend on our services, expertise, laboratories and research. Blood donationappointments can be scheduled at bloodworksnw.org.

AboutClubCorp Since its founding in 1957,Dallas-based ClubCorp has operated with the central purpose of BuildingRelationships and Enriching Lives. The leading owner-operator of private golfand country clubs, city and stadium clubs in North America, ClubCorp isrelentless in its pursuit of providing extraordinary experiences, meaningfulconnections, shared passions and memorable moments for its more than 430,000members. With approximately 20,000 peak-season employees and a portfolio ofover 200 owned or operated golf and country clubs, city clubs, sports clubs,and stadium clubs in 27 states, the District of Columbia and two foreigncountries, ClubCorp creates communities and a lifestyle through itschampionship golf courses, work spaces, handcrafted cuisine, resort-stylepools, tennis facilities, golf lounges, fitness centers and robust programming.

ClubCorpproperties include: Firestone Country Club (Akron, Ohio); Mission Hills CountryClub (Rancho Mirage, California); The Woodlands Country Club (The Woodlands,Texas); Capital Club Beijing; and The Metropolitan in Chicago. You can findClubCorp on Facebook at facebook.com/clubcorp and on Twitter at @ClubCorp.

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Pfizer, NYU working on innovative coronavirus vaccine that could be ready by end of summer – NBC News

Posted: May 7, 2020 at 7:43 pm

Researchers at Pfizer Inc. and New York University are working on a never-before-tried coronavirus vaccine that the pharmaceutical company says could be available by September.

The vaccine, which carries genetic code known as messenger RNA, attempts to reprogram the deadly pathogen rather than manipulate the live virus.

"It is probably the fastest way of having a vaccine available to stem this pandemic, based on the data that I have seen," said Kathrin Jansen, who leads vaccine research for Pfizer.

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The vaccine instructs a person's cells to make proteins associated with the coronavirus without making the person sick. Researchers hope the body's immune system will then kick in, creating the antibodies needed to fight off COVID-19.

"Messenger RNA is something the body produces on its own normally," said Mark Mulligan, chief of infectious diseases at NYU Langone Health. "It's kind of a new thing, but it's really not anything that's too different from what the body does for itself."

But Dr. Peter Hotez, co-director of the Texas Children's Center for Vaccine Development at Baylor University, said no RNA vaccine has been licensed because they have worked well only in laboratory animals.

"Those immune responses have not translated into ... good human immune responses," he said.

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Mulligan said he is optimistic about a trial underway at NYU, but he added that "the data will speak for itself."

"This is the science," he said. "You don't have to have faith or belief. The answer will come from the investigations that we do."

The vaccine is one of dozens under review in the global fight against the pandemic.

Tom Costello is an NBC News correspondent based in Washington, D.C.

Tim Stelloh is a reporter for NBC News, based in California.

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AMC to use stem cell therapy in treating graft-versus-host disease – Korea Biomedical Review

Posted: May 7, 2020 at 7:41 pm

Korean researchers have found a signal transduction system that modulates the treatment of mesenchymal stem cells and immune control functions, opening the way for treating graft-versus-host disease treatment.

Mesenchymal stem cells divide into various cells, have immunomodulatory functions, and are the primary cell sources for stem cell therapy.

Graft-versus-host disease is a fatal disease that leads to death after an allogeneic blood transfusion or bone marrow transplantation. Although there are many clinical trials underway worldwide to treat the symptom, there are no applicable treatments besides alleviating symptoms with high-dose steroids.

The team, led by Professor Shin Dong-myeong of the Department of Biomedical Sciences at Asan Medical Center, discovered that the CREB1 (CAMP responsive element binding protein 1) signaling system activates the treatment and immune control functions of mesenchymal stem cells.

The team administered a therapeutic agent made by upgrading mesenchymal stem cells to graft-versus-host disease mice, and found that it alleviated anorexia symptoms and reduced the weight loss rate by 30 percent while increasing the survival rate by 30 percent.

When developing a cell therapy product, researchers have to cultivate the stem cells in vitro. Thus it is very likely that it will impair stem cell functions due to free radicals generated in the cells. To prevent the deterioration of stem cell function, it is necessary to improve the stem cell function in vitro culture, prevent stem cell oxidation, and increase the antioxidant capacity of the cell itself.

Until now, there was a lack of specific evidence and understanding of how stem cells regulate glutathione, an indicator of antioxidant capacity. Therefore, it was difficult to prevent stem cell dysfunction and oxidation.

Professor Shin's team developed experimental techniques that can monitor and quantify glutathione in real-time and confirmed that the CREB1 signaling system regulated the amount and activity of glutathione.

By activating the CREB1 signaling system, the team found that the process also activated nuclear factor erythroid 2-related factor 2 (NRF2) protein, which maintains the antioxidant capacity of mesenchymal stem cells and the increase of both the expression levels of peroxiredoxin-1 (PRDX1) and glutamate-cysteine ligase modifier subunit (GCLM) protein, which synthesize glutathione and are antioxidant activity indicators.

As a result, the team confirmed that its method was effective in treating the graft-versus-host disease.

"Based on this study, we have secured a technological foundation to advance stem cell treatment by controlling the antioxidant capacity of stem cells," Professor Shin said.

If this technology makes a high-purity and high-quality stem cell treatment, the team expects that it will be a step toward developing a graft-versus-host disease treatment and overcoming various intractable diseases such as nervous system diseases and inflammatory diseases with high medical demand, Shin added.

The results of the study were published in the journal, Science Advances.

corea022@docdocdoc.co.kr

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Heard On Sundial: Reopening Miami-Dade And The Keys, And Stem Cell Treatment For Coronavirus – WLRN

Posted: May 7, 2020 at 7:41 pm

On this Wednesday, May 6, episode of Sundial:

What would reopening look like in Miami-Dade County?

The results of Miami-Dade Countys reopening of parks, marinas and golf courses have been mixed.

WLRN is committed to providing South Florida with trusted news and information. In these uncertain times, our mission is more vital than ever. Your support makes it possible. Please donate today. Thank you.

Over the weekend, hundreds attempted to access boat ramps across South Dade and many were turned away. Also, thousands of people were cited at Miami Beachs South Pointe Park for not wearing protective gear. Officials later closed the park because so few people were adhering to the guidelines.

Listen to today's full show.

"We need to continue testing and retesting and that is going to be crucial to the next stage, opening the county," says Miami-Dade County Commissioner Esteban Bovo, who represents parts of Hialeah and Miami Lakes. "If we don't police ourselves we're going to continue in this cycle."

He joined Sundial to talk with host Luis Hernandez about the possibility of incentivizing residents to take more precautions during the global pandemic.

The Florida Keys have reopened.

Certain businesses like retail shops and restaurants in the Florida Keys were granted permission to reopen on Monday, but to locals only. Monroe County is still closed to visitors.

"It's a cautious start and a good start. I think people are excited to have options," says Rep. State Holly Raschein, R-Key Largo.

The county's checkpoint will remain in place until further notice. It only allows vehicles carrying Keys residents, property owners, workers and deliveries. Screenings will also continue at the Key West International and Florida Keys Marathon International airports.

Read more: Checking In On Keys Checkpoint: Monroe Emergency Management Chief Says 'It's Working'

Raschein, also the chairwoman of the House Agriculture and Natural Resources Appropriations Subcommittee, joined Sundial to discuss the impact of COVID-19 on the Florida Keys economy.

Stem cell treatment for coronavirus using umbilical cords.

Doctors and researchers are working hard to develop antiviral medication amid the coronavirus pandemic. In South Florida, a new coronavirus treatment that uses stem cells from umbilical cords is being tested now.

Dr. Camillo Ricordi, the Director of the Diabetes Research Institute and the Cell Transplant Center at the University of Miami Miller School of Medicine, joined Luis Hernadez to talk about how this treatment may help those sick with coronavirus.

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Coronavirus Update: Baptist Hospital Patient Credits Stem Cell Treatment With Saving Her Life – CBS Miami

Posted: May 7, 2020 at 7:41 pm

MIAMI (CBSMiami) The U.S. Food and Drug Administration gave Baptist Health approval to test a stem cell treatment on COVID-19 patients and so far its come back with positive results.

The treatment has proven successful with three patients.

One of those patients, Ruth Ramirez says it saved her life.

Ramirez was discharged from the hospital on Friday afternoon.

They saved my life. They definitely saved my life, said Ramirez.

Ramirez recently received stem cells from an umbilical cord known as mesenchymal cells.

Mesenchymal stem cells have the ability to reduce cytokine levels, said doctor Guenther Koehne.

Baptist Hospital says patients like Ramirez showed a reduction of their oxygen requirement from 100% to less than 50% within days of the infusion, accompanied by a significant reduction in levels of various key circulating inflammatory markers.

I couldnt breathe. I had a fever a headache I was nauseous, said Ramirez.

Ruth, an employee of the Miami Cancer Institute, tested positive for COVID-19 back on April 7th. She was admitted to the ICU and ended up on a ventilator fighting for her life.

Knowing she may lose consciousness she gave her sister power of attorney. That is when doctors Koehne and Javier Perez Fernandez approached the family about this FDA approved experimental therapy.

Im a person who jumps. I jump with hope with the best outcome there is on the other side. I think she took that into consideration with my characteristic and said Ruth would probably do this.

According to friends, Ruth was in ICU for three weeks, on a ventilator, and unable to breathe on her own.

All that time, she was away from her two small kids. That was several days ago.

On Friday, she was discharged.

To be here in this room, alone, and not being able to hold them. It was hard you know its hard.

As soon as they told me that I was going home I was like what?? And that I tested negative again I was like wait!! That changed my mood completely

Still fuzzy on the timeline, Ruth says shes unsure where along the way she received the treatment but is thankful for the doctors and wants others to know there is hope.

You know I hear the bells here all the time the eye of the tiger thats the song that you walk out of when you come out with coronavirus. Its such a pleasure hearing it all the time now. More than I heard it yesterday.

Not only did the doctors step up, but so did her co-workers who set up this Ruthie-strong go fund me page to help with bills and expenses.

They also helped take care of her family.

They would send food to them. Groceries. My kids were taken care of my sister was taken care of. She didnt have to leave from the house.

Theyre just amazing.

The University of Miami is also working on a clinical trial using mesenchymal cells which we reported on in April.

Click here if you would like to donate to her GoFundMe page.

RELATED:Drive-Through Testing LocationsTrack The Spread Of The Coronavirus In Real TimeTips To Protect Your Vehicle While It Sits Unused During Coronavirus Stay-At-Home Ordercoronavirus

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Mike Tyson, 53, reveals he had stem cell research therapy and hadnt hit bags for 15 YEARS before returning t – The Sun

Posted: May 7, 2020 at 7:41 pm

MIKE TYSON revealed how he has started training again having not thrown a punch for a staggering 15 years - and is being aided by stem-cell research therapy.

The Baddest Man on the Planet, who hung up his gloves in 2005 following defeat by Kevin McBride, wouldn't elaborate on why he was having the treatment but added that it was 'really wild what scientists can do'.

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Tyson was having an Instagram chat with basketball legend Shaquille O'Neal when he revealed that he had been training for the previous three days after 15 years away - and his new health regime.

Iron Mike said: "You know what I had done? I had stem-cell research therapy.

"I feel like a different person but I can't comprehend why I feel this way. It's really wild what scientists can do."

Stem-cell therapy is the use of stem cells to treat or prevent a disease or condition that usually takes the form of a bone marrow transplantation.

He did not reveal what the exact condition was that was being treated.

Despite letting the gloves gather dust in the corner, it didn't take long for Iron Mike to show off that lethal punching power.

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The 53-year-old delighted fans in lockdown by uploading a viral video of him laying into a punchbag with his trademark speed and power.

Tyson's weight ballooned after retiring following battles with drug addiction and depression.

But he has since partnered with a new trainer, MMA coach Rafael Cordeiro, to kick-start his training after sensationally revealing his 15-year break.

During their chat, basketball legend O'Neal revealed how he ached for three days after playing with his sons.

Tyson responded: "That's just because you haven't done it for a while.

WHAT IS STEM CELL TREATMENT USED FOR?

Stem cell transplants are carried out when bone marrow is damaged or isnt able to produce healthy blood cells.

It can also be used to replace damaged blood cells as the result of intensive cancer treatment.

Here are conditions that stem cell transplants can be used to treat:

"If you continue to do it consistently you'll be back to normal.

"It's just like me, I haven't boxed or hit the bag for 15 years - it has been three days so far and I feel incredible."

Tyson, who has a 50-6 record, is reportedly gearing up for a sensational return amid plans to compete in exhibition bouts for charity later this year.

He told rapper T.I. last month: "I've been hitting the mitts for the last week.

"That's been tough, my body is really jacked up and really sore from hitting the mitts.

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"I've been working out, I've been trying to get in the ring, I think I'm going to box some exhibitions and get in shape.

"I want to go to the gym and get in shape to be able to box three or four-round exhibitions for some charities and stuff.

"Some charity exhibitions, make some money, help some homeless and drug-affected motherf****er like me."

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Researchers Convert Astrocytes to Neurons In Vivo to Treat… : Neurology Today – LWW Journals

Posted: May 7, 2020 at 7:41 pm

Article In Brief

A mouse study shows that select transcription factors to the striatum can effectively and safely convert astrocytes to neurons to treat Huntington's disease.

Delivering two transcription factors to the striatum in a mouse model of Huntington's disease can safely convert astrocytes into neurons with high efficiency, according to a new study in the February 27 issue of Nature Communications.

The neurons grow to and wire up with their targets in the globus pallidus and substantia nigra, and remaining astrocytes proliferate to replace those that have been converted. The treatment extends the lifespan and improves the motor behavior of the mice.

What is exciting about this study is that the authors have clearly made cells that do what they are supposed to do, namely replace dying neurons in existing circuits, said Roger Barker, PhD, professor of clinical neuroscience and honorary consultant in neurology at the University of Cambridge and at Addenbrooke's Hospital, who was not involved in the work. I think the challenge of scaling up this strategy to the human Huntington's disease brain is pretty substantial, but nonetheless, this is an important discovery.

The new study, led by Gong Chen, PhD, builds on discoveries beginning in the mid-2000s showing that a small number of exogenously applied transcription factors could transform skin fibroblasts into stem cells, which could then be further converted to become virtually any cell type. That discovery was quickly followed by advances in direct reprogramming, in which one cell type is directly converted into another, skipping the stem cell intermediate.

Most of that work has taken place in vitro, and most attempts to use the strategy therapeutically have depended on transplantation of stem cells or newly converted cells.

We tried stem cell transplants to the mouse brain 10 years ago, but we couldn't find a lot of functional neurons, said Dr. Chen, professor at Guangdong-Hong Kong-Macau Institute of CNS Regeneration of Jinan University in Guangzhou, China.

It was also clear that anything you do in vitro, you eventually have to transplant, and that didn't seem to be a very promising technology, so I said, Let's try this in vivo, and put transcriptions factors directly into the mouse brain.

Dr. Chen initially tried introducing the transcription factor neurogenin 2, but the efficiency of conversion of astrocytes to neurons was very low, so he turned to the transcription factor NeuroD1, which Dr. Chen's group had previously shown could convert astrocytes into excitatory glutamatergic neurons.

In the current study, in order to generate GABAergic neurons, the team combined NeuroD1 with another transcription factor, D1x2, based on previous work showing its importance for generating GABAergic neurons.

The team packed the genes for the transcription factors into a recombinant adeno-associated virus vector (rAAV 2/5) and used an astrocyte-specific promoter to drive the transgene expression so that it preferentially expresses in astrocytes. They first injected the vector into the normal mouse striatum.

Surprisingly, this strategy worked very well at high efficiency, Dr. Chen said. After seven days, all transfected cells expressed astrocyte markers, indicating a high level of specificity in the vector. Of those cells, 81 percent co-expressed the two transcription factors. By 30 days, 73 percent of the cells expressing the transcription factors now expressed neuronal, rather than astrocytic markers, and were primarily GABAergic in character.

Next, Dr. Chen asked whether the remaining astrocytes could repopulate to replace those lost to conversion. Using immunostaining for astrocytes and neurons, as well as other techniques, the team found that the neuron/astrocyte ratio was unchanged, and that some remaining astrocytes could be found at different stages of cell division, suggesting the process facilitated astrocyte proliferation.

Dr. Chen then turned to the R6/2 mouse, the most common mouse model of Huntington's disease. He treated mice at 2 months of age, just as they began to show motor symptoms

As in the wild-type mice, astrocytes were converted to GABAergic neurons at high efficiency without altering the neuron/astrocyte ratio. The researchers observed similar results in a less-severe HD mouse model as well. Treated mice had only about half the degree of striatal atrophy as untreated mice. The converted neurons still contained aggregated huntingtin protein, but less than in native neurons, and similar to the reduced amount found in astrocytes in the mouse brain.

The real test of any cell therapy in neurodegenerative disease is whether the new cells can link into the existing circuits and provide functional benefit, feats that have been hard to achieve with transplanted fetal cells or stem cells.

Examining striatal slices from the treated mice, Dr. Chen found that the converted neurons displayed electrical properties largely identical to those of normal neurons, including resting potential, action potential threshold, firing amplitude, and firing frequency. They integrated into local circuits and behaved similarly to the native neurons around them. By tracking a marker contained in the AAV gene construct, they showed that converted neurons projected axons to the two basal ganglia targets of medium spiny neurons in the striatum, the globus pallidus and the substantia nigra.

Finally, Dr. Chen found that stride length and travel distance were both significantly improved in treated mice, though still falling below those of wild-type mice, and lifespan was significantly extended.

There were no hints of tumors in the mice, Dr. Chen noted. He suggested that in situ conversion is likely intrinsically safer in this regard than using stem cell-derived neurons, since a proliferative astrocyte is being converted into a non-proliferative neuron, with no residual pool of unconverted and potentially tumorigenic stem cells. We are actually reducing the tumor risk, he said.

Why the converted neurons developed appropriate neuronal connections is an important unanswered question, Dr. Chen said. He suggested there were two important factorsfirst, the astrocytes from which they arose are likely developmentally related to neighboring neurons, and thus may express similar position markers that help guide them to the right targets, just like the native neurons. Second, those remaining neurons may also provide guide tracks for the newly growing axons.

This conversion technique is not limited to Huntington's disease, he stressed, noting that his team last year published a paper showing promise in ischemic stroke, and work is underway to test its potential in Alzheimer's disease, Parkinson's disease, spinal cord injury, and ALS. He is also moving on to testing in non-human primates, setting the stage for eventual human trials.

I think eventually we will want to correct the Huntington's mutation as well, Dr. Chen said, for instance by using CRISPR, but he pointed out that while that strategy can repair diseased neurons, it cannot make new ones, like astrocyte-to-neuron conversion can.

This study is really elegantly done, commented Veronica Garcia, PhD, who has studied astrocytes derived from induced pluripotent stem cells from Huntington's disease patients as a postdoctoral scientist working with Clive Svendsen, PhD, in the Regenerative Medicine Institute at Cedars-Sinai Medical Center in Los Angeles.

The conversion efficiency is similar between wild-type and disease models, suggesting that the disease process is not interfering with the conversion, she said.

Astrocyte depletion does not seem to be a problem, at least in the short term, but Dr. Garcia noted there is a limit on the number of divisions astrocytes appear able to undergo, after which they lose the ability to proliferate. That may be a problem for chronic treatment, she suggested. Nonetheless, these results really look promising for therapeutic development.

The concept of trying to reprogram cells in situ to take on the phenotype of the cells that are lost is not new, commented Dr. Barker, but being able to do it with any degree of efficiency, to make enough cells to make a significant difference, has been problematic. For that reason, and because the cells grow to their target sites and make connections, these results are surprising.

A major hurdle for clinical trials, he noted, will be scaling up to the human striatum, which has approximately 100 times the volume of that in the mouse. Delivering the vector to such a large volume will be a significant challenge, he said, along with determining whether this approach will really work in a disease that affects many different brain structures such as in HD.

Dr. Chen is co-founder of NeuExcell Therapeutics Inc, which will develop clinical trials in the future. Drs. Barker and Garcia disclosed no conflicts.

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Characterization and Immunomodulation of Canine Amniotic Membrane Stem | SCCAA – Dove Medical Press

Posted: May 7, 2020 at 7:41 pm

Alessandra de Oliveira Pinheiro,1 Valria M Lara,1 Aline F Souza,1 Juliana B Casals,2 Fabiana F Bressan,1 Paulo Fantinato Neto,1 Vanessa C Oliveira,1 Daniele S Martins,1 Carlos E Ambrosio1

1Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of So Paulo, Pirassununga, So Paulo, Brazil; 2Private Veterinary Practice, Pirassununga, So Paulo, Brazil

Correspondence: Carlos E AmbrosioDepartment of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of So Paulo, FZEA- Av. Duque de Caxias Norte, 225, ZMV, Pirassununga 13635-900, So Paulo, BrazilTel +55 19 3565-4113 Email ceambrosio@usp.br

Purpose: Amniotic membrane stem cells have a high capacity of proliferation, cell expansion, and plasticity, as well as immunomodulatory properties that contribute to maternal-fetal tolerance. Owing to the lack of research on human amniotic membrane at different gestational stages, the canine model is considered ideal because of its genetic and physiological similarities. We aimed to characterize the canine amniotic membrane (CAM) cell lineage in different gestational stages and evaluate the expression of immunomodulatory genes.Materials and Methods: Twenty CAMs from early (20 30 days) (n=7), mid- (31 45 days) (n=7), and late gestation (46 63 days) (n=6) stages were studied. The cell features were assessed by cell viability tests, growth curve, colony-forming units, in vitro differentiation, cell labeling for different immunophenotypes, and pluripotent potential markers. The cells were subjected to RT-PCR and qPCR analysis to determine the expression of IDO, HGF, EGF, PGE2, and IL-10 genes.Results: CAM cells exhibited a fibroblastoid morphology and adherence to plastic with an average cell viability of 78.5%. The growth curve indicated a growth peak in the second passage and we obtained an average of 138.2 colonies. Osteogenic, chondrogenic, and adipogenic lineages were confirmed by in vitro differentiation assays. Cellular immunophenotyping experiments confirmed the presence of positive mesenchymal markers (CD90 and CD105) and the low or negative expression of hematopoietic markers (CD45 and CD34). Qualitative analysis of the immunomodulatory functions indicated the expression of the IDO, HGF, EGF5, and PGE2 genes. When stimulated by interferon-gamma, CAM cells exhibited higher IDO levels throughout gestation.Conclusion: The CAMs from different gestational stages presented features consistent with mesenchymal stem cell lineage; better results were observed during the late gestation stage. Therefore, the gestational stage is a key factor that may influence the functionality of therapies when using fetal membrane tissues from different periods of pregnancy.

Keywords: canine stem cells, immunomodulation, fetal annexes

This work is published by Dove Medical Press Limited, and licensed under a Creative Commons Attribution License.The full terms of the License are available at http://creativecommons.org/licenses/by/4.0/.The license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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