What is Mitochondrial Transplantation?

In the last ten years or so, scientists have discovered, through in vitro (test tubes and culture dishes) and in vivo (within living organisms) studies, that mitochondria can be transplanted from one cell to another, one tissue to another, and from one animal to another. Scientists hope to apply these methods for both primary mitochondrial disorders and for acquired mitochondrial dysfunctions in age-related diseases such as Parkinson’s, dementia including Alzheimer’s and cardiovascular disease.

Although far from ready for large-scale human use, mitochondrial transplantation still requires significant research and testing but holds great promise in providing a viable therapy option for many patients, including primary mitochondrial disease patients, in the future.

Mitochondrial transplantation is an elaborate process; hence, we have tried to simplify the process and minimize medical and scientific terminology to best describe this technique. Mitochondrial transplantation begins by taking a tissue sample (typically muscle tissue) from a donor or from an area of the body where tissues are not affected by damage or disease. Mitochondria are isolated from this tissue sample. The isolation process can be complicated and needs to be done rapidly to ensure the mitochondria remain intact and viable. It’s reported that isolating and preparing mitochondria for transplantation can take anywhere from 2 hours to under 30 minutes, depending on the process used and the amount of mitochondria needed (1).

Currently, there are some limitations in the isolation process. Isolation is limited by a narrow time frame where isolated mitochondria can only stay active and stored on ice for approximately 1-2 hours. This means that isolation and delivery require a short time frame, which demands rapid and not time-consuming surgeries (2).

Once isolated, the mitochondria can be evaluated in several ways, for example, using a combination of fluorescent dye and probes that help illuminate mitochondria microscopically. An ATP assay (ATP is the energy-carrying molecule that fuels cells) can identify and assess viable mitochondria in a transplant batch. Once evaluated, the viable mitochondria are then ready to be transplanted, by injection or infusion, into the bloodstream or into impaired or damaged cells, tissues or organs (3).

Although Mitochondrial transplantation has not been used to treat patients with primary mitochondrial disease, it is currently being studied in cells, animals (such as mice), and humans. More recently, preclinical studies have assessed mitochondrial transplantation as a technique to slow or reverse kidney, retinal, sepsis, brain, or heart damage, to name a few.

Mitochondrial transplantation has been and continues to be investigated in patients with myocardial ischemia (lack of blood flow to the heart impacting functioning, causing heart muscle damage) and reperfusion injury (cell dysfunction or death following restored blood flow to damaged tissue).

At the moment, mitochondrial transplantation has not been used to treat individuals with primary mitochondrial disease. One of the reasons that such studies are more challenging is that they require mitochondria obtained from a donor rather than being taken from a healthy region of the patient’s body. Little work has been done on the donor requirements of mitochondrial transplantation; however, studies involving mouse models have led to speculation about the best approaches in humans, but there are no clear criteria yet.

When considering mitochondrial transplantation and looking for donor sources, if there are areas of the body not affected by damaged or diseased tissues, it’s possible to take a tissue sample from an unaffected area. Then isolate, evaluate and transplant the mitochondria into cells, tissues or organs that have sustained damage or are diseased. In the case of primary mitochondrial disease, all of a patient’s tissues and organs contain genetically impaired mitochondria. For primary mitochondrial disease patients, these techniques will likely need mitochondria from a donor.

Mitochondrial transplantation has been tested in small studies. However, there need to be more studies conducted to determine what type of benefits mitochondrial transplantation will have in managing or treating primary mitochondrial disease. In regards to risk, some studies have shown unwanted inflammatory responses to transplantation from non-related donors. Because of the possible complications, it is recommended to consider a donor who is part of the patient’s genetically close family (4). However, other studies have noted that transplanted mitochondria do not present any evident organ or systemic immune, autoimmune or inflammatory responses (5).

An example of where mitochondrial transplantation has been used is in myocardial ischemia–reperfusion injury in pediatric patients. Myocardial ischemia occurs when there is not enough blood flow to the heart muscle; therefore, the heart muscle cannot function properly. When the blood supply to tissues, muscles or organs is restricted, there is a shortage of oxygen being delivered, which can cause tissue cells to become dysfunctional or even die (6). In the first clinical application, mitochondrial transplantation was used in pediatric patients who suffered myocardial ischemia–reperfusion injury. Mitochondria were transplanted into affected areas of the heart, and post-procedure, patients presented possible improvements in cardiac function compared to similar patients who were not treated with mitochondrial transplantation (7).

Researchers do not seem to fully know the extent of the risks and benefits of this therapy yet but hope to make it possible for future patients to benefit from mitochondrial transplantation.

Thank you for taking the time to learn about mitochondrial transplantation. We kindly ask you to set aside a few moments to complete this survey; it should take no more than 4 minutes to complete. This survey helps us understand a little bit about yourself,  your insights and your opinions on this topic.

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  1. McCully JD, Del Nido PJ, Emani SM. Mitochondrial transplantation for organ rescue. Mitochondrion. 2022 05; 64:27-33. PMID: 35217248.
  2. Tian-Guang Zhang, Chao-yu Miao, Mitochondrial transplantation as a promising therapy for mitochondrial diseases, Acta Pharmaceutica Sinica B, Volume 13, Issue 3, 2023, Pages 1028–1035, ISSN 2211-3835, https://doi.org/10.1016/j.apsb.2022.10.008.
  3. Tian-Guang Zhang, Chao-yu Miao, Mitochondrial transplantation as a promising therapy for mitochondrial diseases, Acta Pharmaceutica Sinica B, Volume 13, Issue 3, 2023, Pages 1028–1035, ISSN 2211-3835, https://doi.org/10.1016/j.apsb.2022.10.008.
  4. Tian-Guang Zhang, Chao-yu Miao, Mitochondrial transplantation as a promising therapy for mitochondrial diseases, Acta Pharmaceutica Sinica B, Volume 13, Issue 3, 2023, Pages 1028–1035, ISSN 2211-3835, https://doi.org/10.1016/j.apsb.2022.10.008.
  5. McCully JD, Del Nido PJ, Emani SM. Mitochondrial transplantation for organ rescue. Mitochondrion. 2022 05; 64:27-33. PMID: 35217248.
  6. Cleveland Clinic. “Myocardial Ischemia: Causes, Symptoms and Treatment.” Cleveland Clinic, my.clevelandclinic.org/health/diseases/17848-myocardial-ischemia. 
  7. A. Guariento, B. Pikarski, A. Ferraro, D. Harrild, D. Zurakowski, P.J. del Nido, J.D. McCully, S.M. Emani. Autologous Mitochondrial Transplantation for Cardiogenic Shock after Ischemia-Reperfusion Injury. J. Thorac. Cardiovasc. Surg., 162 (2021), pp. 992-1001, 10.1016/j.jtcvs.2020.10.151