Augmenting intercellular mitochondrial transfer for tissue repair and rejuvenation.

Cells exhibit innate reparative communication, enabling the exchange of bioactive molecules and, in some cases, entire organelles. Harnessing this endogenous process of intercellular organelle transfer represents an emerging therapeutic paradigm for restoring cellular function in diseases driven by organelle dysfunction. Mitochondrial transfer has gained prominence for its ability to restore bioenergetic capacity, mitigate oxidative stress, and rescue metabolic function in cells with impaired mitochondrial activity. Given that genetic or acquired defects in mitochondrial function are associated with diverse pathologies, including neurodegeneration, cardiovascular diseases, metabolic disorders, skeletal muscle defects, immune dysregulation, and age-associated decline, mitochondrial transfer offers broad therapeutic potential. Mitochondrial transfer seeks to deliver functional mitochondria to injured cells to reestablish metabolic competence. However, insufficient organelle trafficking and limited control over transfer dynamics remain critical barriers to clinical translation. Recent biotechnological developments aimed at enhancing donor-recipient connectivity, increasing mitochondrial availability, and modulating transfer machinery have begun to address some of these key challenges. This review highlights recent advances in mitochondrial transfer bioengineering, emerging therapeutic applications, and key challenges that must be resolved to enable clinical deployment.