Healthy mitochondria, the tiny cellular structures often touted by high school biology teachers as “cell power plants,” are necessary for generating energy in the body, but new research suggests that mitochondria are just adenosine triphosphate. (ATP) supports the idea that it is more than that. pump machine. For about a decade, scientists have been experimenting with implanting these tiny organelles to heal damaged hearts and other tissues. However, the role mitochondria play in the healing process remains a mystery.
Lance Becker, a resuscitation medicine researcher at the Feinstein Institute for Medical Research in Manhasset, New York, said:
A recent study in rats, published March 16, found that BMCmedicine, Becker and his colleagues found that a single vascular injection of mitochondria after resuscitation from cardiac arrest improved both survival and neurological outcome. Within just 15 minutes of injection, the researchers saw improvements in rats’ lactate and glucose levels, biomarkers associated with tissue healing and neurological recovery, and some of these mitochondria reached the brain. I found evidence. The authors of the study found that transplanted mitochondria are also present in several other organs, such as the kidney. This suggests that the organelle migrated from the injection site and was taken up by various tissues throughout the body.
“It’s great that they were able to put it into nerve cells,” says James McQuarrie, a cardiac surgery researcher at Boston Children’s Hospital who was not involved in the study. added that he had never seen mitochondria migrate so far from the injection site. says McCully.
In humans, cardiac arrest is fatal in 90% of cases, and 10% of survivors often suffer neurological damage. The evidence that injected mitochondria can migrate into the brain of animals “opens up a whole new field of treatment for patients suffering from neurological deficits and neurotrauma.” [head and spin injuries]’ says McCurry.
In mitochondrial transplantation, organelles are harvested from intact muscle and injected near damaged tissue or into blood vessels. Blood carries functional mitochondria to tissues where they are absorbed, accelerating the healing process. Increased accessible energy (in the form of ATP) presumably helps the body heal, but Becker believes organelles may also contribute in other ways. It may be sending signals to induce , alter metabolism, or coordinate the activity of existing host mitochondria, he says.
Some of the earliest studies on mitochondrial transplantation began in animal models at Boston Children’s Hospital. Researchers found that heart tissue that failed to heal properly often contained cells with damaged mitochondria, as it was impractical to directly repair existing damaged organelles. , McCully and his colleagues decided to try introducing healthy mitochondria to take over energy production and initiate repair. In 2015, after experiments in pigs, Boston Children’s Heart Surgeon Sitaram, his Emani and McCurry, conducted the first human trial in infants with rare complications not addressed by existing treatments after heart surgery. was carried out. Over the course of three years, he worked with 12 patients and the technique restored healthy cardiac function in eight of her babies’ hearts.
One of the great therapeutic mysteries is whether functioning mitochondria themselves are directly responsible for recovery outcomes, or whether other proteins and molecules, such as the lipids and carbohydrates that make up mitochondria, have an effect. That’s it. To figure out what happens after mitochondrial injection, Becker and his team put his 33 rats into cardiac arrest for 10 minutes and then resuscitated them. During cardiac arrest, animals experienced tissue damage due to oxygen and nutrient deprivation throughout the body, including the brain.
Becker and his team then injected one of the three solutions into the rat’s hind limb vein. Freshly isolated mitochondria from donor rats, frozen and thawed mitochondria from donor rats, or mitochondria-free buffer. The frozen mitochondrial solution contained the same proteins, DNA, and carbohydrates that make up the organelles, but the mitochondria themselves were not fully functional due to freezing damage, Becker explains. If the injection of C. also helped the rats heal, it suggests that mitochondrial components, rather than functioning mitochondria themselves, were driving the recovery process.
The team found that the survival rate of the rats was significantly increased compared to the other two groups when the animals received an injection of fresh mitochondria. Ten of the 11 rats given were still alive, but only 6 of the 11 rats in each group given one of the other two mixtures survived long. Moreover, rats fed fresh mitochondria had better neurological function and cerebral blood flow than animals in other groups.
Becker’s team also marked some of the transplanted mitochondria with a fluorescent dye and found them in rat brain, kidney, and spleen 24 hours after treatment. However, the team does not know the specific pathways from the bloodstream to these locations.
Christoph Maack, who studies cellular defects in heart failure at the University Hospital of Würzburg, Germany, is skeptical that such transplants introduce functioning mitochondria into cells, despite new research. “While there are many studies showing the benefits of this method, we are not convinced that these benefits can be achieved by mitochondria entering the cell and functioning there. Previously, we conducted studies suggesting that they swell and rupture in the bloodstream as a result of calcium overload in the extracellular chemical environment.
As researchers continue to explore the mechanisms behind the efficacy of mitochondrial transplantation, many are pushing forward to discover more areas where this technology could be useful. Since the first mitochondrial transplantation into the brain, other laboratories have begun trials in humans, including stroke patients. Emani says: [organ] transplant world. He and his colleagues are seeking approval from the U.S. Food and Drug Administration to test how mitochondria can revive harvested organs deemed unsuitable for transplantation into other humans. We aim to
Treating common conditions such as cardiac arrest and stroke with mitochondrial transplantation requires treatment as quickly as possible, but specially trained scientists extract mitochondria from human muscle for injection. Instead, Becker might maintain a mitochondrial bank similar to a blood bank, containing organelles readily available to hospitals from volunteer donors. It’s not yet clear what criteria make a good mitochondria donor, says Becker, but organelles can be produced from laboratory-grown cells grown in culture dishes. have a nature
“Ideal is the cell source of mitochondria that grows in every hospital,” says Becker.
