Mitochondrial transplantation as a form of therapy to improve mitochondrial function in aged tissues has barely started as a going concern, and only a few patients have been treated in early studies conducted to date. Yet once the protocols for manufacture and quality control become widely known, availability will likely spread quickly through the medical tourism community, made up of clinics with staff already experienced in the similar techniques used in the provision of stem cell therapies and exosome therapies. Certainly, the research community has already moved on to debating how to improve delivery of mitochondria via a range of potential approaches, and that there will soon enough be an industry hungry for such improvements is assumed to be the case.
Despite the central role of mitochondrial dysfunction in disease progression, current therapeutic strategies remain largely indirect and insufficient for restoring damaged mitochondrial networks. Mitochondrial transplantation introduces a conceptually distinct approach by directly supplying healthy mitochondria to injured cells, shifting mitochondrial medicine from molecular modulation toward organelle replacement and laying the foundation for organelle-level therapy. The concept of mitochondrial transplantation is supported not only by therapeutic need but also by the natural biology of intercellular mitochondrial transfer. Early studies demonstrated that mitochondria or mitochondrial DNA can move between mammalian cells and rescue aerobic respiration in cells with nonfunctional mitochondria.
However, endogenous mitochondrial transfer is spatially restricted, context-dependent, and difficult to control therapeutically. Therefore, the clinical translation of mitochondrial transplantation requires engineered systems that can reproduce the protective and selective features of natural transfer while enabling scalable, stable, and targetable delivery. Early mitochondrial transplantation studies largely relied on the direct administration of isolated free mitochondria; however, this approach was limited by the rapid loss of mitochondrial activity in the extracellular environment, immune-mediated clearance, and inefficient delivery to target tissues. Free mitochondria are intrinsically fragile once removed from the intracellular environment. During isolation, storage, circulation, and uptake, mitochondria are exposed to mechanical stress, osmotic fluctuation, calcium overload, oxidative damage, and extracellular stress, all of which can compromise membrane potential and respiratory competence.
To overcome the limitations of free mitochondrial administration, engineered delivery has become a central determinant of mitochondrial transplantation efficacy. Collectively, recent advances have shifted mitochondrial transplantation from the simple administration of isolated organelles toward carrier-assisted and target-oriented delivery systems. These strategies can be broadly categorized into surface-engineered mitochondria, cell-mediated mitochondrial transport, vesicle-encapsulated mitochondrial delivery, and cell-type-targeted mitochondrial transplantation.
Link: https://doi.org/10.1016/j.scib.2026.08.058
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