The past, present, and close future of mitochondria as a therapeutic agent

Mitochondria have new functions beyond what happens exclusively inside the cell. These new functions include being an extracellular factor for cell-to-cell communication and regeneration, an immunoregulator, and a new therapeutic agent. Scientists, physicians, and entrepreneurs were inspired by the endosymbiotic origin of mitochondria and how they can be transferred through tunneling nanotubes and exist extracellularly inside microvesicles or free of a membrane cover (FreeMitos) to develop a new subcellular drug. This inspiration led to the development of artificial transfer/transplant of mitochondria (AMT/T) techniques based on the isolation of mitochondria and their transfer to damaged cells and tissues. These techniques include the “ex vivo transfer to cells,” the in situ administration at the wounded site, aerosolized compositions, and the mix of mitochondria with a hydrogel matrix. These techniques showed evidence of therapeutic benefits from in vitro to clinical studies. In this chapter, we provide an analysis of the past behind the use of AMT/T and a perspective of its close future based on ongoing clinical trials and patents. New findings on the physiology of extracellular mitochondria and the mechanisms behind their therapeutic potential are continuously being described. However, these discoveries seem to be behind the already granted patents and the diversity of protected applications of AMT/T. We evidence an increase in the development of more effective forms of AMT/T and clinical trials where our work summarizes these key points to further develop this therapeutic option.