Multipotent Stromal Cell Extracellular Vesicle Distribution in Distant Organs after Introduction into a Bone Tissue Defect of a Limb

Igor Maiborodin; Aleksandr Shevela; Michael Toder; Sergey Marchukov; Natalya Tursunova; Marina Klinnikova; Vitalina Maiborodina; Elena Lushnikova; Andrew Shevela

doi:10.3390/life11040306

Multipotent Stromal Cell Extracellular Vesicle Distribution in Distant Organs after Introduction into a Bone Tissue Defect of a Limb

Life (Basel). 2021 Apr 1;11(4):306. doi: 10.3390/life11040306.

Authors

Affiliations

¹ Institute of Molecular Pathology and Pathomorphology, Federal State Budget Scientific Institution "Federal Research Center of Fundamental and Translational Medicine", Ministry of Science and Higher Education of the Russian Federation, Akademika Timakova st., 2, 630117 Novosibirsk, Russia.
² The Center of New Medical Technologies, Institute of Chemical Biology and Fundamental Medicine, The Russian Academy of Sciences, Siberian Branch, Akademika Lavrenteva str., 8, 630090 Novosibirsk, Russia.
³ International Center of Dental Implantology "iDent", Sibrevkoma st., 9b, 630007 Novosibirsk, Russia.

Abstract

When administered intravenously, extracellular vesicles derived from multipotent stromal cells (MSC EVs) immediately pass through the lungs along with the blood and regularly spread to all organs. When administered intraperitoneally, they are absorbed either into the blood or into the lymph and are quickly disseminated throughout the body. The possibility of generalized spread of MSC EVs to distant organs in case of local intratissular administration remains unexplored. However, it is impossible to exclude MSC EV influence on tissues distant from the injection site due to the active or passive migration of these injected nanoparticles through the vessels. The research is based on findings obtained when studying the samples of lungs, heart, spleen, and liver of outbred rabbits of both sexes weighing 3-4 kg at various times after the injection of EVs derived from MSCs of bone marrow origin and labeled by PKH26 into an artificially created defect of the proximal condyle of the tibia. MSC EVs were isolated by serial ultracentrifugation and characterized by transmission electron microscopy and flow cytometry. After the introduction of MSC EVs into the damaged proximal condyle of the tibia of rabbits, these MSC EVs can be found most frequently in the lungs, myocardium, liver, and spleen. MSC EVs enter all of these organs with the blood flow. The lungs contained the maximum number of labeled MSC EVs; moreover, they were often associated with detritus and were located in the lumen of the alveoli. In the capillary network of various organs except the myocardium, MSC EVs are adsorbed by paravasal phagocytes; in some cases, specifically labeled small dust-like objects can be detected throughout the entire experiment-up to ten days of observation. Therefore, we can conclude that the entire body, including distant organs, is effected both by antigenic detritus, which appeared in the bloodstream after extensive surgery, and MSC EVs introduced from the outside.

Keywords: bone tissue defect of a limb; exosomes; extracellular vesicles distribution; heart; liver; lungs; multipotent stromal cell extracellular vesicles; spleen.