Recent advances in mitochondrial transplantation to treat disease

Abstract

Mitochondrial transplantation (MT), an innovative regenerative technique widely used to treat diseases caused by mitochondrial dysfunction, shows great promise for clinical application. This procedure can increase the number of mitochondria and improve the function of damaged mitochondria, resulting in increased adenosine triphosphate levels, decreased reactive oxygen species production, improved Ca²⁺ buffering capacity, modulated inflammatory response, and reduced apoptosis to protect cells, thus promoting tissue repair. In this review, we describe research advances in MT over the last five years, focusing on its application in treating various diseases, including ischaemic injuries (of the kidney, heart, lung, and liver), neurodegenerative disorders, spinal cord injury, sepsis, diabetes mellitus, stroke, and ultraviolet radiation injuries, as well as in procedures such as organ transplantation, focusing on instances where MT demonstrated good efficacy. We also cover the application of engineered mitochondria and mitochondrial combination therapies and present the latest advances in improving MT efficiency, as well as the current clinical applications and shortcomings of MT, aiming to provide a theoretical foundation for enhanced MT utilisation in the future.

Keywords: cardiovascular diseases; ischaemia/reperfusion injury; mitochondrial dysfunction; mitochondrial transplantation; neurodegenerative diseases.

Figure 1. The structure of mitochondria. Created with BioRender.com. ATP: adenosine triphosphate; mtDNA: mitochondrial DNA.

Figure 2. Approaches for transplanting exogenous mitochondria into cells. Created with BioRender.com.

Figure 3. Application of mitochondrial transplantation in the treatment of ischaemia/reperfusion-induced renal injury model in rat by renal artery injection. (A–C) Ischaemia/reperfusion was induced by ligature of left renal hilum for 45 minutes. (D) The isolated mitochondria derived from pectoralis major muscle cells already prepared for the transplantation. (E, F) The mitochondria were immediately injected into renal artery using a 32 gauge needle. (G–I) After transplantation, the kidney was returned to abdomen and the anterior abdominal wall was closed with sutures. Reprinted from Jabbari et al.

Figure 4. Role of exogenous mitochondrial transplantation in the treatment of spinal cord injury. Created with BioRender.com. ATP: adenosine triphosphate; ROS: reactive oxygen species.

Figure 5. Mitochondrial transplantation for paediatric patients who required central extracorporeal membrane oxygenation support for ischaemia/reperfusion associated myocardial dysfunction after cardiac surgical procedure. (A) Biopsy of non-ischaemic skeletal muscle for mitochondrial extraction. (B) Injection of autologous mitochondria into the myocardium using an insulin syringe. Reprinted from Emani et al. Copyright 2017 by The American Association for Thoracic Surgery.

Figure 6. Prospects for clinical applications of mitochondrial transplantation. Created with BioRender.com.