Mitochondria Donation by Mesenchymal Stem Cells: Current Understanding and Mitochondria Transplantation Strategies

Abstract

The phenomenon of mitochondria donation is found in various tissues of humans and animals and is attracting increasing attention. To date, numerous studies have described the transfer of mitochondria from stem cells to injured cells, leading to increased ATP production, restoration of mitochondria function, and rescue of recipient cells from apoptosis. Mitochondria transplantation is considered as a novel therapeutic approach for the treatment of mitochondrial diseases and mitochondrial function deficiency. Mitochondrial dysfunction affects cells with high energy needs such as neural, skeletal muscle, heart, and liver cells and plays a crucial role in type 2 diabetes, as well as Parkinson's, Alzheimer's diseases, ischemia, stroke, cancer, and age-related disorders. In this review, we summarize recent findings in the field of mitochondria donation and mechanism of mitochondria transfer between cells. We review the existing clinical trials and discuss advantages and disadvantages of mitochondrial transplantation strategies based on the injection of stem cells, isolated functional mitochondria, or EVs containing mitochondria.

Keywords: cell fusion; extracellular vesicles; isolated mitochondria; mitochondria donation; mitochondria transplantation; tunneling nanotubes.

FIGURE 1

The cell-based (A) and cell-free (B) strategies of mitochondria delivery into recipient cells. A (I)—mitochondria transfer through TNTs, A (II)—mitochondria exchange after cell fusion, B (I)—injection of isolated mitochondria, B (II)—application of peptide conjugated mitochondria, B (III)—delivery of mitochondria encapsulated into EVs.