Fecal Transplants See Success in 90 Percent of Bacterial Gut Infections

Microbiome Renovation

Transplants are a vital part of healthcare, giving tens of thousands of people in the United States a new lease on life. While organ transplants are relatively commonplace, a new form of transplantation is emerging to fight a life-threatening infection — one that impacts nearly half a million Americans, and is annually responsible an estimated 15,000 to 30,000 U.S. deaths.

However, these doctors aren’t transplanting an organ; they’re taking the fecal matter of ultra-healthy people and transplanting it into patients battling a Clostridium difficile (C. diff) infection, which causes severe diarrhea in sufferers.

Yellowish clusters of Clostridium difficile, the bacterial gut infection that fecal transplants have proven robust at treating.
Clostridium difficile. Image source: Wikimedia Commons/CDC

The Infectious Diseases Society of America (IDSA) has issued new guidelines that promote the use of fecal transplants to treat this infection. Poop transfers, if you will, may sound like a surreal way of treating any kind of illness, let alone a bacterial infection. Yet C. diff infections are most often the result of antibiotic use, which decimates the natural defenses of a healthy gut microbiome.

Fecal transplants are meant to take the microbiomes of healthy donors and allow them to flourish in the recipients, killing any C. diff infection along the way.

In the new guidelines, the ISDA notes a success rate nearing 90 percent of transplants, though long-term data on the effectiveness of the treatment is not yet available. A new registry is being developed by the American Gastroenterological Association, with support from the National Institute of Allergy and Infectious Diseases, to track 4,000 patients for ten years in hopes of gathering this kind of data. Thus far, weight gain has been reported in some transplant patients. STAT reports that some are concerned depression, allergies, diabetes and asthma — all believed to be associated with the gut microbiome — could also be transferred.

Prior to the advent of fecal transplants, patients had to undergo surgery to remove infected colons if other options were exhausted. The new guidelines will empower healthcare providers to utilize fecal transplant treatments in more cases, especially in patients who have been resistant to traditional antibiotic treatments.

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Artificial Organs: We’re Entering an Era Where Transplants Are Obsolete

No More Heart Transplants

Around the world, lists of patients in need of an organ transplant are often longer than the lists of those willing (and able) to donate — in part because some of the most in-demand organs for transplant can only be donated after a person has died. By way of example, recent data from the British Heart Foundation (BHF) showed that the number of patients waiting for a heart transplant in the United Kingdom has grown by 162 percent in the last ten years.

Now, 50 years after the first successful heart transplant, experts believe we may be nearing an era where organ transplantation will no longer be necessary. “I think within ten years we won’t see any more heart transplants, except for people with congenital heart damage, where only a new heart will do,” Stephen Westaby, from the John Radcliffe Hospital in Oxford, told The Telegraph.

Westaby didn’t want to seem ungrateful for all the human lives saved by organ transplants, of course. On the contrary, he said that he’s a “great supporter of cardiac transplantation.” However, recent technological developments in medicine may well offer alternatives that could save more time, money, and lives.

“I think the combination of heart pumps and stem cells has the potential to be a good alternative which could help far more people,” Westaby told The Telegraph.

An Era of Artificial Organs

Foremost among these medical advances, and one that while controversial has continued to demonstrate potential, is the use of stem cells. Granted, applications for stem cells are somewhat limited, though that’s down more to ethical considerations more than scientific limitations. Still, the studies that have been done with stem cells have proven that it is possible to grow organs in a lab, which could then be implanted.

Science has also made it possible to produce artificial organs using another technological marvel, 3D printing. When applied to medicine, the technique is referred to as 3D bioprinting — and the achievements in the emerging technique have already been quite remarkable.

Thus far, scientists have successfully 3D-bioprinted several organs, including  a thyroid gland, a tibia replacement that’s already been implanted into a patient, as well as a patch of heart cells that actually beat. All of these organs were made possible by refinements to the type of bioink; one of many improvements to the process we can expect to see in the years to come, as there’s now an institution dedicated to advancing 3D bioprinting techniques.

Other technologies that are making it possible to produce synthetic organs include a method for growing bioartificial kidneys, the result of a study in 2016.

For his part, Westaby is involved in several projects working to continue improving the process: one uses stem cells to reverse the scarring of heart tissue, which could improve the quality of life for patients undergoing coronary bypass. Westaby is also working on developing better hardware for these types of surgical procedures, including inexpensive titanium mechanical heart pumps.

Together with 3D bioprinting such innovations could well become the answer to donor shortages. The future of regenerative medicine is synthetic organs that could easily, affordably, and reliably be printed for patients on demand.

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A New Gene Engineering Method Could Allow Us to Grow Organs for Transplants

A Chemical Approach

Making an organism’s genome — its entire genetic structure, from scratch — is already possible, but so far it’s only been successful in tiny bacterial genomes and in a portion of a yeast genome. Several researchers are working on synthesizing the entire human genome, but our current methods are limited because of their dependence on enzymes.

Now, a team of researchers from the University of Southampton in the U.K., working with colleagues from the University of Oxford and DNA synthesis firm ATDBio (based in Southampton and Oxford), propose a new method that could surpass these limitations.

In a study published in the journal Nature Chemistry, the researchers showcased a purely chemical technique for gene assembly. It uses an efficient and rapid-acting chemical reaction called click chemistry that puts together multiple modified DNA fragments into a gene — a process called click DNA ligation.

Image Credit: US Department of Energy

“Our approach is a significant breakthrough in gene synthesis,” University of Southampton Chemical Biology Professor and Lead Researcher Ali Tavassoli said in a press release. “Not only have we demonstrated assembly of a gene using click-chemistry, we have also shown that the resulting strand of DNA is fully functional in bacteria, despite the scars formed by joining fragments.”

Human Genome Synthesis

Although plans to synthesize the human genome from scratch have been received with mixed feelings and ethical considerations, its appeal comes from the possibilities it has to offer. According to GP-write, an international effort working on engineering large genomes, applications of DNA synthesis include growing transplantable human organs from scratch, engineering viral immunity and cancer resistance, and even allowing for more efficient and cost-effective drug development and testing.

Ethical quandaries notwithstanding, synthetic DNA is promising. With it, we could be looking at better ways to treat DNA-based diseases, or edit them out altogether — ultimately, extending human life or even potentially creating it from scratch, so to speak. “Genome synthesis will play an increasingly important role in scientific research,” Tavassoli explained. He believes their approach will make it more possible.

A shortcoming of current methods involves the extensive use of enzymes, which can’t be incorporated into certain sites that control the expression (i.e., the switching “on” or “off”) of genes. This so-called epigenetic information can be crucial to better understand biological processes, e.g., cancer, which couldn’t be cured too soon.

“The synthesis of chemically modified genes, which we have achieved by a radical new approach, will become ever more important as the effects of epigenetically modified DNA on gene expression become clear,” study co-author Tom Brown said in the press release.

Furthermore, the chemical method could also greatly accelerate the synthesis of larger DNA strands, producing larger quantities of a single gene. “We believe our purely chemical approach has the potential to significantly accelerate efforts in this vitally important area, and ultimately lead to a better understanding of biological systems,” Tavassoli added.

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Transplants of Genetically Modified Pig Organs for Humans Could Happen Within Two Years

Xenotransplantation

This year, novel organ transplant procedures have been getting a fair amount of attention. While some may seem rather bizarre — like that human head transplant currently in the works — others could be the beginning of a new era in organ transplantation. Chinese researchers have been working on using genetically modified pig organs for human transplantation, and they expect it to be available in the next two years.

Because they closely resemble human organs in terms of size and metabolism, pig organs are considered to be the best animal organs for human transplants — a procedure known as xenotransplantation. Studies involving pig organ transplants have shown considerable benefits, most notably a baboon that received a pig’s heart was able to survive for three years.

In order to confirm these effects, researchers from more than 10 institutes in China have asked permission from the government to conduct human clinical trials use pig organs for transplants. These trials are part of a a national xenotransplantation project funded by the Chinese central government.

Piggy Organ Bank

China seems to be leading the way in this field, producing more genetically modified pigs than any other country. For pig organ transplants to work, modifying pigs by removing certain genes are necessary to prevent the human immune system from rejecting the donated organsThe South China Morning Post (SCMP) reports that cloning farms in China produce a total of 1,000 cloned pigs a year, according to one researcher.

That’s potentially a huge pig organ bank, assuming the government manages to approve clinical trials soon. For Zhao Zijian, director of the Metabolic Disease Research Centre at Nanjing Medical University in Jiangsu, the government seems to be taking too long.

An Exponential Timeline of Organ Transplants
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“We have patients dying from organ failure and their desperate relatives pleading for them to have the chance to live,” Zhao, who’s also a senior scientist at a xenotransplantation lab, told the SCMP. “But when we turn to the authorities in charge of approving the clinical trials, all we get is silence. We understand it must be very hard for the government to make a decision, but it’s time we got an answer.”

Pig organs could speed up the process of getting transplants. In China, for instance, over 300,000 patients require organ transplants, but only less than 10,000 organs are donated each year. Moving forward, initiative when it comes to coming up with the necessary regulations are needed. “Someone has to take the first step – whether it’s the US Food and Drug Administration or the China Food and Drug Administration,” Zhao said.

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A New Technique Could Revolutionize Organ Transplants

Deep Freeze

A group of scientists from the University of Warwick has taken inspiration from nature for a new research project that could greatly improve the process of human organ transplantation.

An Exponential Timeline of Organ Transplants
Click to View Full Infographic

The researchers have developed a new synthetic antifreeze that mimics the properties of natural antifreeze proteins (AFPs). These proteins are produced naturally by extremophile species in cold environments, which need to be able to moderate the formation and spread of ice in order to survive.

The Warwick team’s synthetic antifreeze is iron-based, and they attribute its ability to slow the growth of ice crystals to the separation of the iron complex into regions with either water-loving or water-hating characteristics, imitating the composition of APFs found in nature.

Heart of Ice

This synthetic antifreeze could be useful for a wide range of applications, from making airplane wings less susceptible to the cold to helping produce smoother ice cream. However, it could have a major impact on something far more significant than dessert: organ transplants.

After organs are removed from a donor, they have to be iced in order to prevent them from dying off before they reach their recipient. This process is problematic, as organs typically only last for four hours before being rendered unusable. Sixty percent of hearts and lungs donated for transplants are discarded each year due in part to this short shelf life.

If organs were frozen, and not simply put in cold storage, they could last longer, but under normal circumstances, organs simply can’t survive the freezing process — cells are liable to shrivel up or even collapse entirely, the matrices that connect cells together might be torn apart, and blood vessels can disintegrate entirely.

Ice crystals are the cause of all of these major problems. If the Warwick researchers’ synthetic antifreeze can thwart the growth of these crystals, it could make it possible for surgeons to freeze organs without the associated negative effects. This would make transplants safer and add a lot more flexibility to the process in terms of timing and transport.

Most significantly, this ability to freeze organs could dramatically decrease the number of donations that are wasted as a result of their short timeframe for use. Data from the U.K. suggests that if half of the wasted organs were actually used, transplant waiting lists could be eliminated within just a couple of years.

This project hasn’t yet moved to trials using human organs, so real-world use is still far off, but the research has the potential to give people waiting for transplants a much better shot at getting the organ donation they need.

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