Healthy mitochondria, those tiny cellular structures that high school biology teachers often tout as “cell power plants“, are a necessity for producing energy in the body, but new research supports the idea that they are more than just adenosine triphosphate (ATP) pumping machines. For about a decade, scientists have experimented with transplanting these microscopic organelles to treat damaged hearts and other tissues, and they’ve seen a handful of positive results in human trials.But the role mitochondria play in the healing process remains a mystery. .
“There’s a whole field of basic science that’s just begging, like, ‘Please, please, please come and explore here,'” says Lance Beckerresuscitation medicine researcher at the Feinstein Institutes for Medical Research in Manhasset, NY
In a recent study in rats published on March 16 in BMC MedicineBecker and his colleagues found that a single injection of mitochondria into a blood vessel after resuscitation from cardiac arrest may increase both survival rates and neurological outcomes. Within just 15 minutes of injection, the researchers observed improvements in the rats’ lactate and glucose levels – biomarkers associated with tissue healing and neurological recovery – and found evidence that some of these mitochondria reached the brain. The study authors also found the transplanted mitochondria in several other organs, such as the kidneys, suggesting that the organelles had moved from the injection site and had been taken up by various tissues throughout the body.
“It’s great that they were able to get it into neural cells,” says the Boston Children’s Hospital cardiac surgery researcher. James McCully, who did not participate in the study. He adds that in his previous work, he had not seen mitochondria move so far from the injection site. “It’s a big step forward, and it would be great if this systemic application could be translated into a larger animal model,” McCully said.
In humans, cardiac arrest is fatal in 90% of cases, and the 10% of people who survive often have neurological damage. Evidence that injected mitochondria could travel to animal brains “opens up a whole new area of treatment for patients with neurological abnormalities and neurotrauma.” [head and spin injuries]McCully says.
In mitochondria transplantation, organelles from uninjured muscle are harvested and injected near damaged tissue or into a blood vessel. The blood carries the functional mitochondria to the tissues, where they are absorbed, and then the healing process accelerates. While an increase in accessible energy — in the form of ATP — likely helps the body heal, Becker suspects organelles might also contribute in another way. The new mitochondria could also send signals to trigger cellular repair, alter metabolism, or coordinate the activity of existing host mitochondria, he says.
Some of the earliest research into mitochondria transplantation began in animal models at Boston Children’s Hospital, where researchers noticed that heart tissue that couldn’t heal properly often contained cells with damaged mitochondria. Because it was not possible to directly repair existing damaged organelles, McCully and his colleagues decided to try introducing healthy mitochondria to take over energy production and initiate repair. After experiments on pigs, in 2015 McCully and heart surgeon Sitaram Emani from the Boston Children’s carried out THE first human trials on infants who had suffered from rare complications after heart surgery that could not be treated with existing treatments. Over the course of three years and 12 patients, the technique restored healthy cardiac function in the hearts of eight babies.
One of the great mysteries of therapy is whether the functional mitochondria themselves are directly responsible for recovery results or whether other proteins and molecules, such as the lipids and carbohydrates that make up the mitochondria, have a impact. To unpack what happens after mitochondria are injected, Becker and his team put 33 rats into cardiac arrest for 10 minutes and then resuscitated them. During cardiac arrest, the animals suffered tissue damage due to lack of oxygen and nutrients throughout their bodies, including their brains.
Next, Becker and his team injected one of three solutions into the veins of the rats’ hind legs: freshly isolated mitochondria from donor rats, frozen and thawed mitochondria from donor rats, or a buffer solution without mitochondria. The frozen mitochondria solution contained the same proteins, DNA and carbohydrates that make up organelles, but the mitochondria themselves were no longer fully functional due to damage from freezing, Becker says. If these injections also helped the rats recover, that would suggest that the building blocks of mitochondria, and not the active mitochondria themselves, were driving the recovery process.
The team found that the rats’ survival rates increased significantly, compared to the other two groups, when the animals were given infusions of fresh mitochondria. Three days after the cardiac arrests, 10 of the 11 rats that received fresh mitochondria were still alive, whereas only six of the 11 rats in each of the groups that had received one of the other two mixtures survived that long. Additionally, rats that received the fresh mitochondria had better neurological function and cerebral blood flow than animals in other groups.
Becker’s team also labeled some of the transplanted mitochondria with a fluorescent dye and found them in the rats’ brains, kidneys and spleens 24 hours after the procedure. But the team does not know their specific blood flow path to these locations.
Christophe Mack, who studies cellular defects in heart failure at Würzburg University Hospital in Germany, is skeptical that such transplants introduce functional mitochondria into cells, despite new research. “There are many studies that show the benefits of the method, but we are not convinced that these benefits can be achieved by mitochondria entering and functioning in cells,” he says. In 2020, Maack conducted a study suggesting that before mitochondria enter heart muscle, they swell and burst in blood as a result of calcium overload in the chemical environment outside the cells.
As researchers continue to explore the mechanism behind the effectiveness of mitochondria transplants, many are also moving forward to discover other areas where the technique may be useful. Since the first mitochondria transplants in infants, other labs have started human trials, including in stroke patients. And according to Emani, “the next real opportunity for us will be in the [organ] transplant world. He and his colleagues aim to gain approval from the US Food and Drug Administration to test how mitochondria could revive harvested organs that would otherwise be deemed unsuitable for transplant into another human being.
For mitochondria transplants to treat common conditions such as cardiac arrest and stroke, which require the fastest treatment possible, it may not be practical to wait for a specially trained scientist to extract mitochondria from muscle. of a person and prepares them for the infusion. Instead, Becker imagines that a hospital could maintain a mitochondria bank, similar to a blood bank, containing organelles readily available from volunteer donors. It’s not yet clear what criteria would make someone a good mitochondria donor, Becker says, but the organelles could be generated from cells grown in the lab and grown in dishes.
“Ideally, we would have a cellular source of mitochondria growing in every hospital,” says Becker.