Abstract
Mitochondrial transplantation is a rapidly developing field of medicine, which may soon emerge as a novel therapeutic approach to restore cellular function following injury from a wide range of diseases. It was relatively recently discovered that mitochondria are highly mobile organelles that transit within cells and travel between cells routinely. They are known to play a critical role in cellular energy and disease. Many conditions, from acute events like cardiac arrest, heart attack, and stroke, to chronic diseases such as neurodegeneration, diabetes, and aging, involve mitochondrial dysfunction. Give this background, the idea of using mitochondrial transplantation as a purposeful medical therapy has gained significant momentum.
We tested this concept in an animal model of cardiac arrest that has a high mortality using traditional resuscitation therapies. We found that intravenous injection of live, functional mitochondria immediately as circulation is returned to pulseless animals, led to a 91% survival rate with good neurologic function, compared to approximately 50% in controls. Further research revealed that transplanted mitochondria exhibit preferential uptake, with significant accumulation in injured brain cells following ischemia, but almost no uptake in normal tissues. This suggests that mitochondria may possess the ability to specifically target damaged areas via some unknown mechanism, now under investigation. Additional studies are ongoing.
At this time human mitochondrial transplantation studies are accelerating. They currently involve isolating mitochondria from a patient’s own tissue for pilot studies in conditions like heart attack, pediatric cardiac surgery, and stroke, with early positive results. Like many very new therapies, there are significant unanswered questions and challenges. A particularly significant challenge is the scalability of current tissue harvesting methods. The proposed solution involves developing bioreactors to grow mitochondria at scale, aiming to create a universal donor mitochondrial product that could be readily available in emergency departments, administered by paramedics, and utilized in chronic disease clinics for diverse conditions. To advance the field of mitochondrial transplantation more rapidly into human use, the field needs more investment in the research, bioengineering, and clinical trials. The cellular mechanisms of how mitochondrial transplantation actually becomes effective is highly speculative and much of this science remains unknown. The future is likely to see a shift in mitochondrial medicine from rare interventions to routine care, restoring bioenergy to cells via mitochondrial transplantation may emerge as a potent new therapy at the near horizon of medicine.
Prof. Lance Becker, MD
Dr. Becker is a leading figure in emergency medicine, critical care and resuscitation science – his translational research spans laboratory studies, animal models and human therapies. For more than 25 years, he has advanced CPR quality, AED use, cardiac arrest care, therapeutic hypothermia and community-based systems of care.
His cellular research has defined mechanisms of reperfusion injury, mitochondrial oxidant generation, ischemia-related responses, apoptotic activation, cytoprotection and hypothermia protection. He has received numerous honors, teaching awards and patents, mentored many researchers, organized major scientific meetings and is an elected member of the Institute of Medicine/National Academy of Medicine.
Dr. Becker joined Northwell Health in 2015 as chair of emergency medicine at North Shore University Hospital and Long Island Jewish Medical Center, professor and chair at the Zucker School of Medicine at Hofstra/Northwell, and investigator at the Feinstein Institute for Medical Research, Institute of Bioelectronic Medicine. Before Northwell, Dr. Becker founded resuscitation centers at the University of Pennsylvania and the University of Chicago/Argonne National Laboratory. He received his medical degree from the University of Illinois College of Medicine.