by Ruggiero Corcella
A research by the University of Turin and Wake Forest University (USA) on a damaged kidney has been published in the Annal of Surgery, the results of which bode well
When it comes to transplants, the blanket is always short: the number of patients on the waiting list for an organ is still high. There are various strategies to remedy the shortage of raw materials: first of all, increase the number of donors. And then the experimentation of forms such as xenotransplantation (organs taken from animals), regenerative medicine and artificial organs as well as mitochondria transplantation.
The sector that currently seems most promising, however, is that of organ regeneration. As regards the lungs, for example, Professor Shaf Keshavjee of the Lung Transplant Center of the University of Toronto (Canada) has developed a sophisticated device called Ex vivo lung perfusion (EVLP or pulmonary perfusion) which makes it possible to understand whether a marginal lung maintains a good functional reserve and can therefore be implanted in a patient.
For about fifteen years, the path of mitochondria transplantation has also been on its way. The University of Turin and Wake Forest University in Winston Salem, North Carolina have just published su Annals of Surgerythe most important journal of surgery in the world, a research on the transplantation of mitochondria on damaged kidney cells whose results bode well.
I study
The two teams are led by Benedetta Bussolati, full professor of Laboratory Medicine, Department of Molecular Biotechnology and Health Sciences at the University of Turin, and by Giuseppe Orlando, associate professor of Surgery and Regenerative Medicine at Wake Forest University, linked by a ten-year collaboration in the field of renal tissue regeneration. The Turin group conducted the first in vitro experiments, studying the effect of isolated mitochondria on damaged kidney cells and demonstrating how it is useful for increasing cellular energy and reducing the stress of damage.
Based on these data, Wake Forest has developed a model closer to the clinic, demonstrating that when a kidney compatible with the human kidney is damaged, the direct injection of healthy mitochondria into the artery is able to repair the damage and activate signals of functional recovery.
What are mitochondria
Mitochondria are the energy powerhouse of our cells, the functioning of which requires the presence of intact and healthy mitochondria. Under stress, the cell’s mitochondrial heritage is damaged, and therefore the cell runs the risk of malfunctioning. Fortunately, mother nature has developed a mechanism that allows cells to overcome this problem, called mitochondrial transfer, through which the malfunctioning cell can acquire new, healthy and intact mitochondria from the environment or from other cells, and then resume normal function explains Professor Orlando.
Since it has now been demonstrated that virtually all diseases are associated with mitochondrial damage, it has recently been thought of replicating this physiological mechanism and proposing it as a real therapy. In practice, healthy mitochondria are taken from cultured cells or tissue from organ donors, and injected into the diseased tissue or organ. Technically, this therapy is called a mitochondrial transplant, he adds.
The pioneer of this procedure
The pioneer of this new field of medicine is Professor James McCully, a cardiac surgeon at the Boston Children’s Hospital, a hospital affiliated to Harvard University. McCully state among the very first researchers to study the phenomenon, clearly demonstrating that the administration of healthy and functional mitochondria to a damaged or diseased tissue or organ can restore the initial state of health. In the wake of these results, a few years ago he received from the FDA (Food and drug administration, the regulatory agency of the United States) the authorization to conduct the first clinical study in this regard, in patients suffering from severe heart disease, with promising results.
Professor McCully has already experimented with mitochondria transplantation on 11 patients, eight of whom survived. The data has been reported in various publications and, although there is still a long way to go, the study is considered a milestone in modern medicine, because it lays the foundations for the application of a therapy that could be proposed, in the future, for the treatment of a myriad of clinical conditions.
Transplant data
One of the fields of medicine that could benefit most from this new therapy in the short term, solid organ transplantation underlines Professor Bussolati who is also president of the Italian Society for Extracellular Vesicles (EVIta).
As mentioned at the beginning, today there is a need for many more organs than can be transplanted. For example: in the world, according to data from the Global Observatory on Donation and Transplantation, around 150,000 transplants are carried out every year which must be compared with a population of eight billion people. In 2022, nearly 43,000 transplants were performed in the United States, including approximately 25,000 kidneys, compared to a waiting list of approximately 120,000 patients. In reality, the situation is far more dramatic. In fact, according to a study published in 2014 in Nature Biotechnology, every year 730,000 patients die in the USA from a disease that could be treated with a transplant and the estimate of the real need for transplantable organs would amount to several million in the United States and Europe alone. In Italy, more than 8,000 patients are waiting for an organ transplant, with an average waiting time for a kidney transplant of around 3 years.
Mitochondrial transplantation could be used to repair and regenerate damaged and therefore non-transplantable organs, in order to increase the number of transplants. This result would have two important consequences: bridging the gap between supply and demand, and reducing the mortality of patients on the waiting list. In practice, two extraordinary results, continues Professor Bussolati.
Marginal donors and heart failure donation
To date, organs taken from so-called marginal donors are also used to increase the number of transplants. In the case of kidney transplantation, for example, a marginal donor is considered a donor who has diseases that cause kidney damage, such as diabetes or hypertension, but who still has normal kidney function, says Professor Orlando. Also, in recent years a new type of donation after cardiac death (DCD, donation after cardiac death) has established itself.
In the US, about 40% of kidneys are harvested from DCD donors. This type of donation is characterized by a prolonged phase of ischemia during which the organs are not perfused by the blood properly, and therefore suffer and undergo damage which is all the more pronounced the longer the ischemia lasts. Since mitochondria are damaged during this phase, mitochondrial transplantation could allow the organ to be repaired and regenerated, thus making it transplantable, he concludes.
July 21, 2023 (change July 21, 2023 | 2:47 pm)
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