The Early Years of Mitochondrial Transplantation as a Therapeutic Strategy

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.


The whole mitochondrial transplant concept is really cool. It is really a good news to hear that there are some (pre) clinical studies under way .

I however, didn't really understand whether mito transplants towards the cancer cells help against cancer. Or was it rather a proof of concept ?

Posted by: Cuberat at October 12th, 2021 5:15 PM

Research hs shown that mitochondrial mutations picked up during the generation of iPSC cells leads to those cells rejection on transplantation. So you'd probably need some method of screening the produced mitochondria before use to get any effect.

Posted by: jimofoz at October 13th, 2021 12:46 AM

Wasn't there something about synthetic mitochondria floating around the idea web not too long ago?

Posted by: Matt at October 13th, 2021 2:56 AM

I don't know. The paper talks of mitochondrial replacement of damaged/dysfunctional mitochondria, but transplantation is not replacement, it's adding mitochondria.
Adding functional mitochondria without removing the damaged/dysfunctional ones, sounds very much like the old 'boost ATP output' strategy. The cells produce sufficent amounts of energy and therefore function better.

But does it help with mTOR deregulation caused by dysfunctional mitochondria sending 'panic' signals to the nucleus which in turn upregulates mTOR, even without nutrient/growth factor stimulation? Clearing the damaged/dysfunctional mitochondria looks to me like a better approach.

The effect of fasting or calorie restriction on mitophagy induction: a literature review

'Study on the muscle tissue of subjects after exercise showed that mitophagy was upregulated in the fed state.
Current evidence overwhelmingly suggests that CR and fasting induce mitophagy and mitophagy-related markers. Based on the current evidence that we reviewed here, it could be concluded that fasting or CR has a promising role as a novel and practical approach in the prevention of age-related diseases without any side effects by inducing mitophagy in different organs of the body. '

Posted by: Jones at October 13th, 2021 3:34 AM

@Cuberat, if my reading was correct, then the transfer of mitochondria into mitochondria-less cancer cells is done in order to abolish the cancer cells' resistance to oxidative stress (including that deployed by the immune system, I assume). Kind of a round about way of going around it, if you ask me, but interesting nonetheless.

Posted by: Mark at October 13th, 2021 6:09 AM


can you link to that research ?

Posted by: Cuberat at October 13th, 2021 8:38 AM

@cuberat - Here is the uni press release and a link to the nature paper.

New Clues on Stem Cell Transplant Rejection Revealed in Study (2019):

The paper in nature:
De novo mutations in mitochondrial DNA of iPSCs produce immunogenic neoepitopes in mice and humans (2019):

Posted by: jimofoz at October 13th, 2021 12:13 PM


As usual, in biology nothing is simple

Posted by: Cuberat at October 14th, 2021 8:37 AM

Thanks for your continued coverage of mitochondrial transplantation. (Disclosure: I'm CEO of Mitrix).

We think that mitochondrial transplantation is already naturally being done within the body - systems of distribution and perhaps even "rationing" of undamaged mitochondria in order to convey longevity, an outgrowth of a billion years of evolutionary optimization of mitochondria.

We're hoping that as the research progresses, we will find more and more potential access points and thus new potential interventions or therapeutics.

It's very early in the science, but very exciting too.

Posted by: Tom Benson at October 17th, 2021 12:43 AM
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