Effect of Erythropoietin on Morphofunctional Properties of Mesenchymal Stem Cells

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Cell Technologies in Biology and Medicine,  No. 3,  November,  2020

Effect of Erythropoietin on Morphofunctional Properties of Mesenchymal Stem Cells A. P. Lykov, M. A. Surovtseva, I. I. Kim, N. A. Bondarenko, and O. V. Poveshchenko

Translated from Kletochnye Tekhnologii v Biologii i Meditsine, No. 3, pp. 209-216, September, 2020 Original article submitted May 6, 2020 We studied the effect of erythropoietin on the morphofunctional status of bone marrow mesenchymal stem cells in patients with coronary heart disease. It was shown that the duration of cell exposure with erythropoietin had different effects on the expression levels of adhesion molecules, erythropoietin receptors, and co-expression of the erythropoietin receptor and common β-chain of cytokines, apoptosis/necrosis, and the cell cycle. In most cases, erythropoietin increased proliferation, migration, and NO production by “aged” mesenchymal stem cells (passage 8) and passage 4 mesenchymal stem cells grown during the previous 3 passages in the presence of 33.4 U/ml erythropoietin. Erythropoietin increased the expression of the autophagy marker LC3B in mesenchymal stem cells grown in the presence of erythropoietin in the culture medium. Thus, long-term culturing of mesenchymal stem cells in the presence of erythropoietin in the culture medium increased their resistance to adverse microenvironment factors — oxidative stress and hyperglycemia. Key Words: mesenchymal stem cells; erythropoietin; adhesion molecules; apoptosis; LCB3 Mesenchymal stem cells (MSC), a heterogeneous population of progenitor cells with angiogenic, antiapoptotic, and immunomodulatory properties, are used in regenerative medicine as an alternative treatment for inflammatory and degenerative diseases [7,11,13]. Despite the capacity of MSC to migrate to the pathological focus and differentiate into different directions, only a small part of transplanted MSC can actually reach the lesion. In addition, MSC viability in the focus of inflammation is significantly affected by the microenvironment, in particular, oxidative stress [3,23]. The age of MSC donor has a significant impact on the functional potential of MSC: the older is the donor, the lower is the proliferative potential. Aging is associated with exhaustion of the pool of stem cells in the organs and tissues and a decrease in their regenerative potential, which, in turn, impairs the efficiency of treatment Research Institute for Clinical and Experimental Lymphology — Affiliated Branch of Federal Research Center Institute of Cytology and Genetics, Siberian Division of Russian Academy of Sciences, Novosibirsk, Russia. Address for correspondence: [email protected]. A. P. Lykov

with autologous stem cells [16]. Moreover, aging of MSC is accompanied by a decrease in their migration potential and homing [20]. MSC aging in culture (passage 8) leads to loss of fibroblast-like morphology and growth uniformity typical of “young” (passage 4) cells and a decrease in their proliferative potential and CD146 expression [24]. In light of this, the se