MGH doctors perform first-ever live-cell pig skin graft to burn patient – Boston Herald

Burn specialists at Massachusetts General Hospital are the first in the world to successfully use live-cell, genetically engineered pig skin to temporarily close a burn wound in a human patient but the breakthrough has drawn opposition from People for the Ethical Treatment of Animals.

The ultimate holy grail is the end to the worlds organ shortage, that would be the holy grail, this has come at a time when genetic editing is really hot and what we could do in years, we can do in weeks, said Dr. Jeremy Goverman of the MGH Sumner Redstone Burn Service.

The pig tissue, known as xenoskin, was transplanted directly onto a human burn wound next to a larger piece of human skin.

Five days later, surgeons removed the human skin and the pig tissue to see that both grafts were stuck to the wound bed and were indistinguishable from each other.

Following the procedure, the burn wound was then treated further with a skin graft taken from the patients thigh. Healing progressed well and the patient will return to work soon.

The goal is to replace skin with xenoskin thats like it enough that it doesnt get rejected, said Goverman. Down the line we hope to ultimately create something thats not temporary.

The biggest push now is actually decreasing your donor site size and decreasing how much skin you have to harvest, said Goverman.

Patients who receive this type of graft typically have severe burns that require more than one operation and about a week of hospitalization.

Weve been using dressing like this in the past, we just havent been able to use anything with live cells. The live cells have all the appropriate factors that could really stimulate and regenerate and close our wounds for us, said Goverman.

MGH worked with Boston-based XenoTherapeutics, which designed the safety protocols for the special live-pig tissue graft.

Paul Holzer, CEO of XenoTherapeutics said, We have taken a small but unprecedented step in bringing xenotransplantation from theory to therapy, one that we hope will advance this promising field of medicine and benefit patients around the world.

Human skin grafts are subject to a national shortage and can be expensive, therefore using the pig skin can serve as a viable alternative, according to MGH.

But Alka Chandna, vice president of laboratory investigations cases at PETA, said there is no shortage of donated skin grafts.

Its categorically unethical to steal organs from another sentient being whos still using them. Pigs are individuals, not warehouses for spare parts, said Chandna.

Chandna said, Tinkering with the genes of these intelligent, sensitive beings to turn them into organ factories is a waste of lives, time and money and the suffering caused is unimaginable.

The advancement of the procedure reaches back decades to genetically modified pigs that were developed in the 1990s at MGH by Dr. David Sachs.

The modifications removed a gene specific to pigs and not present in humans, allowing the pig skin to appear less foreign to the human immune system.

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Single-Cell Sequencing: Paving the Way for Precision… – Labiotech.eu

Next-generation sequencing techniques to determine an individuals unique genetic code gave rise to personalized treatments. Single-cell sequencing is the next step towards making precision medicine more accurate.

Each cell in our body is unique. Even genetically identical cells can behave differently in response to a certain treatment. With next-generation sequencing, scientists can study how the average cell within a group behaves. However, this can lead to erroneous conclusions.

It is like population surveys which tell us the average American family has 1.2 children. Thats useless. Thats not helpful. Not a single family has 1.2 children, stated Christoph Lengauer, CEO of Celsius Therapeutics, in an interview with STAT News. His company has raised more than 60M to develop precision therapies using machine learning.

Single-cell sequencing, by contrast, can indicate which family has six children, and which has just one and a dog, Lengauer said. Its orders of magnitude more granular.

This is a huge paradigm shift. Single-cell sequencing was recognized as method of the year by Nature in 2013. Since then, the number of publications from both academia and the industry exploded.

In recent years, there has been a shift in the technology available to perform single-cell sequencing. Fluidigm used to hold the bulk of the market with products across the entire workflow but is currently suffering from poor sales due to new competitors.

At the forefront is US-based 10X Genomics, founded in 2012, which registered a 20-fold revenue increase between 2015 and 2017. Its sequencing platform allows large populations of cells to be separated and analyzed with high resolution. The company is also developing a technology to study how cells are positioned in 3D which could be used to see how tumors grow and expand.

Another contender is the alliance between two giants, Bio-Rad Laboratories and Illumina. They announced in January 2019 a joint single-cell sequencing solution that streamlines the whole workflow. Mission Bio, a spin-off from the University of California San Francisco is selling a single-cell sequencing platform that targets clinical applications with a lower price per run compared to its competitors.

Despite the rapid market growth, the use of single-cell sequencing is so far limited to a narrow circle of initiates. Over the past years, academic facilities have started providing single-cell sequencing services to researchers. For example, the technology is used at the Institut Curie in Paris to study cancer cells.

More recently, companies have started working in this area, often using technology initially developed in academia to identify new biomarkers and drug targets. All seem to have a common goal: personalized medicine.

Research on most diseases related to genetic or epigenetic mutations could benefit at some point from single-cell sequencing. There are already scientific publications applying this technology in microbiology, neurology, immunology, digestive and urinary conditions.

Among them, oncology is probably the most promising and mature application. Previously, bulk analysis of cells from a tumor biopsy only gave information on the predominant type of cells. In contrast, single-cell sequencing can provide information about other tumor cells, which might be resistant to a certain therapy and result in a relapse after the first line of treatment.

This technique is highly sensitive and is able to detect rare cell types from limited amounts of sample material. Combined with technology to isolate circulating tumor cells from a blood sample, single-cell sequencing can be used to select patients in personalized medicine trials.

IsoPlexis is one of the very few companies with an advanced program to apply single-cell sequencing to proteomic studies looking at the role of protein expression in cancer. The company is developing a technology to measure the levels of a dozen molecules secreted by immune cells that are primed to recognize and attack a tumor. Last year, this was used to predict, for the first time, the response that a person with blood cancer will have to CAR T-cell therapy. The company claims that it could also be applied to cancer patients treated with checkpoint inhibitor immunotherapy.

Single-cell sequencing can also be combined with CRISPR gene editing to make elaborated large-scale studies of how a genetic modification affects cell behavior. The Austrian company Aelian Biotechnology is combining both techniques to observe gene functions with single-cell resolution, establishing a new paradigm for next-generation CRISPR screening. This approach has broad applications, including identifying novel drug targets or studying unknown mechanisms of actions of drugs.

Either for research or clinical diagnostics, single-cell sequencing remains challenging and is far from being used routinely. One of the main reasons is that single-cell collection is tricky, as the amount of sample material used is low but the analysis still requires a sufficient amount of cells to make sure all cell types are represented. The time it currently takes to complete an experiment is another major concern. Companies developing single-cell sequencing technology need to work on creating streamlined and optimized workflows that limit these problems.

Although experimental methods for single-cell sequencing are increasingly accessible to laboratories, handling the data analysis remains challenging. There are currently limited guidelines as to how to define quality control metrics, the removal of technical artifacts, and the interpretation of the results. With larger experiments, the data analysis burden increases.

Single-cell data requires the analysis of millions of data points for a single tumor, said Andrei Zinovyev, who leads a machine learning project focusing on single-cell data analysis at the Institut Curie in Paris.

There are many software tools developed by academics, mostly available in open source. However, their use is limited to a small community of researchers that have been able to successfully combine advanced bioinformatics and statistical skills with in-depth knowledge of the biological systems they study. Companies such as 10X Genomics and Fluidigm also provide software tools, but this area remains in its infancy and gold-standard tools have yet to be developed.

For single-cell analysis to spread to a broader community, user-friendly analysis tools are needed. In this area, Swiss startup Scailyte is developing an AI-based solution to discover biomarkers from single-cell data, analyzing complex datasets in just a few hours. The US startup Cellarity is also working in this area, seeking to combine single-cell sequencing with artificial intelligence and CRISPR gene editing.

The use of single-cell sequencing is limited due in part to its high cost. Most of the instruments and reagents needed are costly. For someone looking to incorporate single-cell sequencing into their laboratory, 10X Genomics for example sells its instruments for about 70,000. A typical run, including cell isolation and sequencing, can cost anywhere between 3,000 and 10,000 per sample, depending on the number of cells.

Due to the high cost, it is becoming popular for laboratories with the equipment to offer single-cell sequencing and analysis as a service. The US company Mission Bio is tackling this issue, aiming to reduce the cost to between $1,000 and $2,000 for a typical run.

As is mostly the case in any area with a huge market potential, intellectual property can cause conflict, which can negatively impact the development of new technologies. For example, back in 2015, Bio-Rad sued 10X Genomics for patent infringement, and the jury determined it would have to pay 21M in damages. Furthermore, 10X Genomics could not sell their products to new customers, being therefore limited to servicing historical clients with all past and future sales subject to a 15% royalty.

Several months later, the US company Becton Dickinson also sued 10X Genomics. After that, the company decided to build a new piece of equipment to reinforce its intellectual property position. In September, 10X Genomics countersued Becton Dickinson.

The single-cell sequencing market experienced a growth spike between 2017 and 2018 due to several key stakeholders entering the market. But we are only at the beginning. According to most business reports, this market is expected to see a 300% growth, reaching a size of almost 1.4B by 2023.

Competitors are innovating at an insane rate to take the lead, but there is still a long way to go before single-cell sequencing can be widely used. A huge amount of investment would be needed to fully unlock its potential for research, drug discovery, and diagnostics. Nonetheless, the field has momentum and once it tackles the challenges, there is no doubt that single-cell sequencing will pave the way to breakthrough innovations in personalized medicine.

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Prevent the spread of the flu virus – Baylor College of Medicine News

If there is anything we have learned from previous years, its that flu season is unpredictable. However, getting your flu shot now offers the best protection for the entire season, according to an expert at Baylor College of Medicine.

Its difficult to predict the duration and intensity of the flu season, but we know that it will be here and it will have a significant health impact on everyone, said Dr. Pedro A. Piedra, professor of molecular virology and microbiology and of pediatrics at Baylor College of Medicine.

This years flu vaccine includes two updated components to better reflect what flu strains may be circulating this year, the influenza A H1N1 and the influenza A H3N2 components.

The ability to predict what strains will circulate each flu season is not perfect, Piedra said, and, at times, the vaccines dont match well with what is circulating. Despite that, influenza vaccines can have a significant impact on the health of an individual as well as the health of the community, he said.

During last years flu season, multiple viruses circulated. Flu vaccines contain three or four components to protect against multiple viruses.

You could be infected early in the flu season and still be susceptible to other influenza viral infections because they can be entirely different, which is why it is always best to be vaccinated before the flu season begins. Thats when you will get the best protection, Piedra said. Vaccines work best when they are delivered prior to the flu season because it will provide duration of protection through the full season.

Recently, researchers found that the traditional, egg-based influenza vaccine may not protect well against the H3N2 strain, so Piedra recommends seeking out the vaccines that are made from insect cell lines or mammalian cell lines, which may offer better protection against the H3N2 strain and provide comparable protection against the other influenza viruses (influenza A H1N1 and influenza B strains).

Because the flu vaccine is administered at a time when other viral infections are circulating, some people may feel like they have a cold right around the time they receive the vaccine. However, Piedra, who also is with Texas Childrens Hospital, said that it is not related to the vaccine. Its most likely that they were ill with another virus at the time they were vaccinated and didnt know. Some individuals will have soreness or redness at the site of injection. Mild to moderate local reactions are associated with the influenza vaccine. Overall, influenza vaccines are well tolerated and safe in children, adults, pregnant women and older adults.

There can be breakthrough infection, and antivirals are available for those who become infected with the flu virus. Antivirals need to be started within 48 hours of the onset of illness to get the full benefit.

For high-risk individuals, such as older adults or children less than 5 years of age or children and adults with asthma, heart disease, diabetes or other health conditions, Piedra recommends reaching out to their physician before the influenza season on how to best use antiviral drugs if they are infected with the flu. He recommends that they have a plan with their physician on how to get the antiviral drug within 24 hours of the onset of illness.

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HIV Latent Reservoir Forms Near the Time of ART Initiation, Researchers Find – AJMC.com Managed Markets Network

While antiretroviral therapy (ART) can suppress HIV infection, ART cannot completely eradicate HIV, which remains in a latent reservoir in CD4-positive T cells during treatment; discontinuation of ART leads to rapid rebound of the virus. This reservoir forms even when ART is initiated early on in the infection, and while the most widely accepted model of how the reservoir forms involves infection of a CD4-positive T cell as it transitions to a resting state, the dynamics and timing of the reservoirs formation have been largely unknown.

This reservoir forms even when ART is initiated early on in the infection, and while the most widely accepted model of how the reservoir forms involves infection of a CD4-positive T cell as it transitions to a resting state, the dynamics and timing of the reservoirs formation have been largely unknown.

This month, in a paper in Science Translational Medicine, researchers report that they have now identified evidence showing that initial use of ART alters the host environment to allow the formation or stabilization of the most long-lived HIV reservoir that persists for multiple years during treatment.

The researchers used archived pre-ART viremic samples from the CAPRISA 002 cohort, based in South Africa, to establish a temporal record of viral evolution in 9 women who enrolled from the time of their primary HIV infection. Because the patients enrolled prior to initiating ART, the researchers could use the differences in viral sequences to measure different time points.

Using this viral record, the investigators estimated when the viruses had persisted after more than 4 years during therapy and entered the latent reservoir. In most of the patients, the majority of viruses entered the reservoir around the time that therapy was started; 71% of the unique viruses from the post-therapy latent reservoir were genetically similar to viruses replicating just before ART was initiated.

These findings suggest, say the authors, that ART itself alters the host environment by suppressing viral replication to favor long-lived cells, some of which have latent HIV infection.

This comes as a big surprise, said co-senior author Ronald Swanstrom, PhD, professor of biochemistry and biophysics at the UNC School of Medicine, in a statement on the findings. Our work suggests that if we could understand the reservoir-forming process better, we might be able to intervene at the start of treatment to reduce the majority of the reservoir that forms at this time.

According to Swanstrom, combining ART with a drug that inhibits the transition of CD4-positive cells to the memory cell state could help prevent some of the viral reservoir from forming in the first place.

A major goal of current HIV research is to allow people to stop therapy without having the virus come back, Swanstrom said. One strategy to achieve this is to eradicate the latent reservoir. Starting with a smaller reservoir could help make that an attainable goal.

Reference

Abrahams MR, Joseph SB, Garrett N, et al. The replication-competent HIV-1 latent reservoir is primary established near the time of therapy initiation. Sci Transl Med. 2019;11:eaaw5589. doi: 10.1126/scitranslmed.aaw5589.

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Sixteen ASCB Fellows to be welcomed at 2019 meeting of cell biologists this December – Newswise

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Newswise The American Society for Cell Biology (ASCB) is pleased to present its cohort of 16 new Fellows for 2019.

Through the ASCB Fellows program, we acknowledge the scope and diversity of the Societys membership. Our Fellows represent not only an elite group of scientists who have contributed significantly to the body of knowledge about cell biology and to the community of scientists studying the cell, but also individuals who have demonstrated throughout their careers their commitment to the mission of the Society, said Erika Shugart, the chief executive officer for ASCB.

Election as a Fellow of ASCB is an honor bestowed upon ASCB members by their peers. The list of approved Fellow nominees is reviewed and approved by the ASCB Council. The new cohort of ASCB Fellows will be formally recognized before the keynote speech at the 2019 ASCB|EMBO Meeting in Washington, DC, Dec. 7.

The new ASCB Fellows include:

David Asai, Senior Director of Science Education, Howard Hughes Medical Institute

Kerry Bloom, Thad L. Beyle Distinguished Professor and Chair of Biology; Professor of Cancer Cell Biology, University of North Carolina-Chapel Hill

Anthony Bretscher, Professor of Cell Biology in the Department of Molecular Biology and Genetics, Cornell University

Mary Dasso, Senior Investigator, Section on Cell Cycle Regulation, National Institute of Child Health and Human Development, National Institutes of Health

Erin Dolan, Georgia Athletic Association Professor of Innovative Science Education, University of Georgia

Ian Macara, Chair of the Department of Cell & Developmental Biology, Professor of Cell and Developmental Biology, Vanderbilt University

Erika Matunis, Professor of Cell Biology, Johns Hopkins University School of Medicine

David Mitchell, Professor, SUNY Upstate Medical University

Denise Montell, Duggan Professor and Distinguished Professor, University of California, Santa Barbara

Gregory Pazour, Professor of Molecular Medicine, University of Massachusetts School of Medicine

Birgit Satir, Professor in Anatomy and Structural Biology, Albert Einstein Medical College

Susan Strome, Distinguished Professor of Molecular, Cell and Developmental Biology, University of California, Santa Cruz

Vassie Ware, Professor of Molecular Biology and Co-Director of the HHMI Bioscience Program, Lehigh University, Bethlehem, PA

Susan Wente, Interim Chancellor/Provost and Professor of Cell and Developmental Biology, Vanderbilt University

Mark Winey, Dean of the College of Biological Sciences, University of California, Davis

Xin Xiang, Professor of Biochemistry, Uniformed Services University of the Health Sciences, Bethesda, MD

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