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The Early Years of Mitochondrial Transplantation as a Therapeutic Strategy

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Posted 12 October 2021 - 07:22 PM

Mitochondria are the power plants of the cell, generating the chemical energy store molecule adenosine triphosphate (ATP). Throughout the body, mitochondrial function declines with age, leading to corresponding declines in tissue and organ function. This universal malaise appears to be a downstream consequence of the underlying causes of aging. Those causes in some way lead to changes in gene expression that alter mitochondrial dynamics in ways that reduce the efficacy of the quality control mechanism of mitophagy. When not regularly destroyed, worn and dysfunctional mitochondria accumulate, and ATP production suffers.

It is possible to achieve benefits by introducing replacement mitochondria? Won't they just succumb to the same problem due to the aged environment? Eventually, yes, most likely. But studies to date suggest that the benefits of mitochondrial transplantation can large enough and long-lasting enough to be worth pursuing, even if the benefits fade over time.

Cells will readily take up whole mitochondria from their environment, and thus the immediate hurdles are largely a matter of logistics: being able to reliably generate and characterize mitochondria in the vast numbers needed to make a difference to cell function throughout the body. Once that is possible, then a range of further questions can be explored: duration, safety, long-term effects, whether transplanted mitochondrial DNA must match the recipient, or whether it can be improved upon, and so forth. A number of biotech companies, such as cellVie and Mitrix, are working to develop mitochondrial transplantation as a basis for therapies, so the next few years will be an interesting time in this part of the field.

Mitochondrial Dysfunction in Diseases, Longevity, and Treatment Resistance: Tuning Mitochondria Function as a Therapeutic Strategy

It has been shown that mitochondria can be transferred both artificially and under normal physiological state. We can transfer mitochondria as a "cybrid" or treated isolated mitochondria directly into the cells or tissues. We can also transfer mitochondria by co-culture cells as a normal physiological state. Mitochondria transfer from one cell to another cell occurs especially when the mitochondria are injured. Therefore, the mitochondrial transplantation from healthy cells to abnormal cells is thought to be a novel and attractive therapeutic concept. It has been reported that mitochondria and/or organelles transfer between cells through tunneling nanotubes.

Replacement of damaged mitochondria with healthy mitochondria has been developed in order to overcome mitochondrial diseases and mitochondria dysfunctions. It has been shown that mitochondrial transplantation (mtTP) rescues ischemia reperfusion-induced damage and protects the brain from apoptosis. Current clinical and preclinical studies utilizing mtTP have been conducted or are in progress for the treatment of heart ischemia, brain ischemia, sepsis, cancer, acute kidney injury, and theoretically for any disorders in which mitochondria are damaged and disrupted.

We have demonstrated that mitochondria from a non-cancer cell line can be transplanted into cancer cell lines that lack mtDNA (ρ0 cells). This mitochondrial transplantation has been checked using MitoTracker, which can stain mitochondria, and confirmed that the healthy stained mitochondria from fibroblast cells have certainly transplanted into ρ0 cells. Recently, in a clinical trial, it has been shown that mtTP leads to cardio protection. It has been reported that mtTP ρ0 cells have decreased intracellular Fe2+ levels and downregulation of aquaporins. Since aquaporins regulate H2O2 permeability, these cells exhibit H2O2 resistance compared with the non-mtTP ρ0 cells. Thus, mtTP may enhance mitochondrial function that will allow for the rescue of cells and restoration of normal function.

Taken together, these results indicate that mtTP may be an upcoming effective therapeutic option. Therefore, mtTP is a very promising technique, which may be applicable for the treatment of many diseases including cancer. However, mtTP is only in the beginning stages of development, so further investigation will be needed to address various technical and ethical issues.

View the full article at FightAging

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