Potential Applications of Extracellular Vesicles in Solid Organ Transplantation

Abstract

Extracellular vesicles (EVs) play an important role in cell-to-cell communication by delivering coding and non-coding RNA species and proteins to target cells. Recently, the therapeutic potential of EVs has been shown to extend to the field of solid organ transplantations. Mesenchymal stromal cell-derived EVs (MSC-EVs) in particular have been proposed as a new tool to improve graft survival, thanks to the modulation of tolerance toward the graft, and to their anti-fibrotic and pro-angiogenic effects. Moreover, MSC-EVs may reduce ischemia reperfusion injury, improving the recovery from acute damage. In addition, EVs currently considered helpful tools for preserving donor organs when administered before transplant in the context of hypothermic or normothermic perfusion machines. The addition of EVs to the perfusion solution, recently proposed for kidney, lung, and liver grafts, resulted in the amelioration of donor organ viability and functionality. EVs may therefore be of therapeutic interest in different aspects of the transplantation process for increasing the number of available organs and improving their long-term survival.

The Unique Immunomodulatory Properties of MSC-Derived Exosomes in Organ Transplantation

“…Clinical application showed the feasibility of exosomes. Current research focuses on preconditioning the graft before transplantation and preventing ischemia/reperfusion injury to improve the viability of transplanted organs ( 104 , 105 ). In large animal experiments, we can better understand the biological and functional characteristics of MSC-derived exosomes and define the acceptance in allotransplantation.…”

Cellular therapies in organ transplantation

“…One of the challenges would be to isolate these vesicles free from contaminating soluble proteins, as these accumulate in the same fractions as vesicles using conventional centrifugation and filtration techniques [102]. Currently, extracellular vesicles have not been examined in the context of clinical trials, although a number of studies have examined the effect of vesicles on isolated animal and human organs, demonstrating a potential reparative effect of vesicles [103]. In addition to collecting extracellular vesicles from cell culture supernatants, it is possible to generate vesicles from the membranes of MSC or other cell types.…”

Treatment of transplant kidneys during machine perfusion

“…Extracellular vesicles (EVs) are a population of doubled layered membrane fragments released by different types of stem cells and endothelial progenitor cells (EPC EVs) [18]. They differ in size, sedimentation rate and floating density and contain biologically active molecules such as proteins, lipids and nucleic acids (mRNAs, microRNAs and other noncoding small RNAs) [18]. They influence cells via interaction with surface receptors, direct stimulation and by the transferral of proteins and genetic material.…”

“…They influence cells via interaction with surface receptors, direct stimulation and by the transferral of proteins and genetic material. Their properties are beneficial for angiogenesis, extracellular matrix remodelling, regulation of inflammation, cell cycle and proliferation, cell migration and morphogenesis [18]. In experimental models, EVs have been shown to protect against acute and chronic kidney injury [18].…”

“…Their properties are beneficial for angiogenesis, extracellular matrix remodelling, regulation of inflammation, cell cycle and proliferation, cell migration and morphogenesis [18]. In experimental models, EVs have been shown to protect against acute and chronic kidney injury [18]. EVs can home in on damaged cells within the kidney via the peritubular capillaries or glomeruli.…”