[Tanada]

UBC researchers have found a way to convert any blood type to the universal O

The hope is to eliminate the need for compatibility between donor and recipient.

Researchers at the University of British Columbia have found a technique that could make all donated blood compatible with all patients, regardless of the blood type of the donor or the recipient.

UBC biochemist Stephen Withers announced that he and his team had found a way to convert different types of blood into the universally useful O-negative. The research was presented at this week's meeting of the American Chemical Society.

The hope is that this could one day help alleviate chronic shortages of O-negative blood. Earlier this month, Canadian Blood Services made its regular late-summer call for blood donors across the country. With many donors away on vacation, this is one of the times of year when blood can be in short supply.

Finding the tool to convert blood types

Human blood comes in four types: A, B, AB and O. What distinguishes them are tiny sugar molecules on the surface of the red blood cells. A, B and AB blood have distinctive sugar molecules that are recognized by the immune system, so if a patient receives blood of an incompatible type, a dangerous immune reaction against the blood cells can occur.

O-negative blood, however, does not have these sugar molecules, and so is essentially invisible to the immune system, which is why its universally compatible with all recipients.

Your blood type determines who you can donate to, or receive blood from. People with type O negative are considered universal donors as they can donate red blood cells to all other blood type recipients.

The key to making A, B and AB blood universally compatible is to find molecular scissors that can efficiently snip off the sugar molecules. Researchers have been looking for such tools since the early 1980s, with limited success.

Withers' group began searching for an enzyme — a kind of protein that targets specific molecules and cuts them. They suspected there was a natural source for the enzyme they needed in the form of bacterium that might produce it, but the trick was to identify the bacteria.

Initially, they looked to blood-sucking creatures for ideas.

"In the lab, we tossed around various ideas about where there might be bacteria that would degrade blood," Withers told CBC Radio's Quirks & Quarks. "One thinks of things like the leech gut or the mosquito gut, but those are probably a little hard to access."

It turned out, there was a more readily available source: human gut bacteria. Our gut wall is coated with sugar structures called mucins, which on their surface have the same sugar molecules that are found on different types of red blood cells. According to Withers, "It was quite likely that the gut bacteria had evolved the capacity to cleave off some of those sugars to derive energy for themselves. So the human gut microbiome seemed like a good place to look."

A breakthrough discovery

Withers extracted 20,000 different DNA samples from gut bacteria taken from human feces, and discovered a number of them that could produce the enzymes to do the job. From those, he noticed one new class of enzymes that was particularly good at cleaving the sugars.

"It can cleave approximately 30 times more quickly from the previous best candidate that was published a while back, when we did a side-by-side comparison of the two."

Researchers looked at 20,000 different DNA samples taken from human gut bacteria to find the best enzyme to cut the antigens.

This high level of efficiency means less of the enzyme is needed in the blood conversion process. That means lower production costs, but more importantly, it means less of the enzyme needs to be filtered out of the converted blood afterward — a necessary step before transfusion.

"This work is very promising," Dana Devine, chief scientist at Canadian Blood Services, wrote in an email to Quirks & Quarks. "The type of blood donated will likely never be exactly matched to the demand for specific blood groups, but this new technology offers an opportunity to create a 'workaround' for the disproportionate demand for O blood by turning the excess inventory of other blood groups into group O."

Withers attributes his success in this project to new techniques in metagenomics that weren't available to his predecessors. These tools gave him a way to grow gut bacteria DNA en masse and examine the gut microbiome at a grand scale, looking at thousands of candidates at once, which let him cast the net wide to find the best bacteria for the job.

It may be some time, however, before this blood conversion technique makes it out of the lab. Extensive safety tests are still necessary before the converted blood can be approved for use in transfusions.

LINK

[Tanada]

Blood substitute repairs damaged organs hours after heart stops

ale School of Medicine

A procedure that reverses cell damage after the heart has stopped pumping blood may lead to more organ transplants and better treatments for heart attacks and strokes, and one day could even save the lives of people who would currently be considered dead.

The method, which so far has been tested on pigs, involves connecting an animal to a pump that perfuses their bodies with an artificial blood substitute containing oxygen and a mixture of other chemicals to prevent cell death and promote repair processes.

“We have shown that cells don’t die as quickly as we assumed they do, which opens up possibilities for intervention. We can persuade cells not to die,” says Zvonimir Vrselja at Yale School of Medicine.

Currently, people whose hearts are failing may be connected to heart-lung machines, which oxygenate their blood, remove carbon dioxide from it and pump it around the body.

But if someone’s heart stops while they are outside of a hospital, their cells and organs are quickly damaged by the lack of oxygen and their chances of survival plummet. Their blood becomes more acidic from a build-up of CO2 and many damaging substances are released. “The blood is full of all sorts of bad things,” says John Dark at Newcastle University, UK, who wasn’t involved in the work.

The new system, called OrganEx, dilutes the animal’s blood in a 1-to-1 ratio with an artificial blood substitute that carries oxygen, has the correct acidity and has the right levels of electrolytes and other biochemicals. It also has 13 drugs added.

These are either existing medicines or experimental drugs, including compounds that thin the blood to stop small blood vessels getting blocked by clots, drugs that block a cell death process called necroptosis and others that have anti-inflammatory effects.

The blood substitute is also unusual in that it contains no red blood cells, which normally carry oxygen bound to a protein called haemoglobin. Instead, the fluid contains a compound called Hemopure, a form of haemoglobin obtained from cow’s blood.

In 2019, Vrselja and his team reported that their system could reverse signs of cell death when connected to the brains of pigs, four hours after they had been decapitated. In the latest study, they wanted to see if the fluid could help reverse the damage that occurs in other organs after death, and to test it in whole bodies.

The pigs were put to sleep with a general anaesthetic and put on ventilators to control their breathing. Then their hearts were stopped electrically and the ventilators were turned off, at which point they would normally be considered dead.

After 1 hour, the treatments to try to restore cell function began. Six pigs were connected to the OrganEx system and six others were connected to an ordinary heart-lung machine as a comparison, with both groups’ body temperature reduced to 28°C to help reduce damage. There were three further control groups, where the animals were given no treatment.

After 6 hours, the extent of blood flow was measured by injecting dye and doing scans of the animals. The pigs given the OrganEx treatment had better blood supply to their organs than the animals put on a heart-lung machine, in which many of the smaller blood vessels had collapsed.

Tests on cells and tissue samples from the animals showed that those treated with OrganEx had less cell death and had restored cell functioning, judged by measures such as how much glucose they could metabolise.

The team says the first practical use of the system may be in keeping organs for transplants healthy for longer so they can be transported further between deceased donors and people who need them.

Peter Friend at the University of Oxford says the initial results are promising, but the best way to gauge the health of the animals’ organs would be to transplant them into another animal. “That lets you see if they work,” he says. “If they’re going after transplantation, just transplant the organ.”

The system could also potentially be used to help people who have had heart attacks or strokes – when blood supply to the heart or brain, respectively, is reduced – by perfusing either of these organs with the healing fluid. “If it is successful in resuscitating an organ which has suffered an otherwise fatal injury, then potentially this is very exciting,” says Friend.

Stephen Latham, an ethicist at Yale University who was part of the research team, says the more radical use of trying to “reverse death” – for instance, in treating someone some time after their heart has stopped due to drowning – would be much further in the future.

“There’s a great deal more experimentation that would be required,” he says. “The perfusate would have to be adapted to a human body. And you’d have to think about what is the state to which a human being would be restored. If you gave them a perfusate that reversed some but not all of that damage, that could be a terrible thing.”

Newscientist.com

[evilgenius]

Let's hope that doesn't just mean a "radical" advance in how pig farms can operate. Now, they can actually kill their pigs several times before they actually kill them the final time!

[Tanada]

Let's hope that doesn't just mean a "radical" advance in how pig farms can operate. Now, they can actually kill their pigs several times before they actually kill them the final time!

In one way it is kind of scary to me that they let these executed pigs just lay there for a full hour before starting up the heart lung machines and feeding half of them the chemical cocktail just to see what would happen.

The fact that they were able to get at least portions of the organ tissue to revive after so long without oxygen or nutrients being available is on the one hand very surprising and on the other hand kind of terrifying. We know that a human brain deprived of oxygen for five minutes starts to suffer significant loss of cognitive capabilities. Adults revived after twenty minutes have almost always been revived as brain dead, autonomic function only but no higher brain activity. That doesn't mean much with a pig brain, but the ultimate plan for this process is to stabilize human organs for transplant by flooding the body with this chemical cocktail when the family gives permission to use them as a donor for organs and tissue.

We really have no idea what this cocktail might due to human brain tissue. If it works such miracles for hour dead kidneys and livers what will it do for human brains that just got badly bruised in a car accident? A recurrent image in depictions of organ donor fears is being cut up for parts while your brain is still smart enough to know you are being cut up for parts.

I am in favor of people who wish to donate doing so because I know it can vastly improve the life of the recipient, but with this sort of storage technology we take a big step closer to increased pressure from government to make organ donation mandatory rather than voluntary.

Here is my reasoning. Currently organ donations are so precious and rules are so restrictive that frequently a donated organ which has to be implanted within a few hours is given to the person in the most desperate need of a replacement. The problem with this practice is a 45 year old with excellent prospects for surviving the surgery and going on to live an average lifespan is often passed over in favor of a 45 year old who has had organ failure for months or years and whose remaining organs have been damaged by the long term illness that has resulted. Now if this technology turns out to work as described they will be able to take an organ donor, put them on a heart lung machine with this new chemical cocktail and keep them alive for days or even weeks while they look for the best tissue match instead of the most desperate needy person. Under the current system many organs are rejected because the recipient who is most needy is often not the best tissue match with the donor. With more time to evaluate both donor and recipient finding the closest available match would mean the recipient is less likely to reject the transplant and more likely to live a longer more productive life. But that would require a change to the rules about most desperate always being first in line. Once they start changing the rules to most viable being first in line for the donated organs then you get the knock on effect that the donation rate is really causing massive shortages of kidneys, livers and other key organs like the Pancreas. With a Pancreas transplant a diabetic patient could recover completely from the need for insulin and also have massive improvement in overall health from a naturally responsive organ rather than injections that try and meet basic needs. Currently this is not done because a kidney or liver or heart failure will kill the desperate recipient very rapidly and a treatment like Dialysis quite literally costs the government half a million dollar per year per patient. Two kidneys from a donor potentially saves the government a million dollars a year for 10-20 years depending on how well the recipient accepts the new organ.

Because of the demand for kidneys, livers and hearts you see they make up the vast majority of all transplant operations. Something like a Pancreas transplant doesn't save the government much because even at inflated prices in the USA paying for insulin is far less expensive than paying for mechanical dialysis by several orders of magnitude. Occasionally there are lung transplants for things like cystic fibrosis but despite the pleas of the telethon people they are still relatively rare because child organ donation is the rarest form and the shortage of child organs is profound. For an older miner dying of black lung disease they usually never even make it onto the recipient waiting list because they have multiple problems from years of damage reducing oxygen flow to all their organs has caused.

But, if you can keep all those lovely organs alive with a bath of their artificial cocktail indefinitely suddenly there are supplies of lungs and pancreas and all the other "lower priority" transplant tissues available. This is great for the surgeons and I have no problem with people suffering from lung disease getting a transplant, but every change has consequences. People have been conditioned that mainly livers and kidneys are what get transplanted because you can even make a living donation for those organs in relative safety. But a short term bumper crop in new organs will exponentially increase demand with kids dying of lung disease and becoming the face of need leading the way. That vastly increased pressure could easily lead to donation going from voluntary to mandatory because of twelve year old charlie is brain dead from a vehicle collision but his lungs can save both Suzy and Tina from choking to death from cystic fibrosis there is an emotional and rational argument favoring the change.