Mitochondrial donation in translational medicine; from imagination to reality

Abstract

The existence of active crosstalk between cells in a paracrine and juxtacrine manner dictates specific activity under physiological and pathological conditions. Upon juxtacrine interaction between the cells, various types of signaling molecules and organelles are regularly transmitted in response to changes in the microenvironment. To date, it has been well-established that numerous parallel cellular mechanisms participate in the mitochondrial transfer to modulate metabolic needs in the target cells. Since the conception of stem cells activity in the restoration of tissues’ function, it has been elucidated that these cells possess a unique capacity to deliver the mitochondrial package to the juxtaposed cells. The existence of mitochondrial donation potentiates the capacity of modulation in the distinct cells to achieve better therapeutic effects. This review article aims to scrutinize the current knowledge regarding the stem cell’s mitochondrial transfer capacity and their regenerative potential.

Stem cell‐derived mitochondria transplantation: A promising therapy for mitochondrial encephalomyopathy

“…The TNFα/NF‐κB/TNFαip2 pathway is upregulated in response to TNFα 70 ; then, stem cells further promote the formation of TNT 71 . Inflammation by interferon‐γ or lipopolysaccharide has also been shown to promote the expression of M‐Sec proteins associated with TNT formation 72,73 . The Rho‐GTPase Miro1 can facilitate the migration of mitochondria via TNTs between two cells.…”

Membrane nanotubes are ancient machinery for cell-to-cell communication and transport. Their interference with the immune system

“…ongoing via the nanotubes connecting them. In lack of space, here we orient the interested reader to several excellent recent reviews on this subject (Ariazi et al 2017 ; Bagheri et al 2020 ; Buszczak et al 2016 ; Korenkova et al 2020 ; Lou et al 2012a , 2018 ; Sisakhtnezhad and Khosravi 2015 ; Thayanithy et al 2014 ) and next we will focus on intercellular transport via NTs between cells of the immune system (IS) and its effect on the function of the IS.…”

The Role of Mitochondria in Immune-Cell-Mediated Tissue Regeneration and Ageing

“…Mitochondria have been shown to be horizontally transferred between mammalian cells, with the incorporation of mitochondria into the original mitochondrial network of recipient cells, contributing to changes in the bioenergetic profile both in vitro and in vivo [ 121 ]. The transfer of mitochondria may also result in the initiation of stem cell differentiation, reprogramming cells, or activation of signaling pathways.…”

“…The transfer of mitochondria may also result in the initiation of stem cell differentiation, reprogramming cells, or activation of signaling pathways. Mitochondria exchange between cells can occur via tunneling nanotubes (TNTs), EVs, and cellular fusion [ 121 ]. TNT formation was reported in immune cells as well as in neurons, glial cells, and cardiomyocytes [ 122 ].…”

“…Mitochondrial dysfunction is a key event in simulated ischemia/reperfusion (SI/R) injury. In vitro (SI/R) experiments demonstrated that bone marrow(BM)-derived mesenchymal stem cells rescue injured H9c2 cardiomyocytes, via transferring intact mitochondria through tunneling nanotubes [ 121 ]. Recent evidence has shown that in stress response, stromal cells can transfer healthy mitochondria to hematopoietic stem cells (HSC), facilitate HSC bioenergetics shift towards oxidative phosphorylation, and leukocyte expansion [ 125 ].…”