Therapeutic potential of a biomedical cellular product in rats with lower limb ischaemia

Lykov A.P.^1,2, Bondarenko N.A.^1,2, Poveshchenko O.V.^1,2, Kabakov A.V.², Surovtseva M.A.^1,2, Kim I.I.^1,2, Kazakov O.V.², Poveshchenko A.F.^1,2, Yankaite E.V.²

1) Scientific Research Institute of Clinical and Experimental Lymphology, Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences,
2) National Medical Research Centre named after Academician E.N. Meshalkin, Novosibirsk, Russia

Critical ischaemia of lower limbs is a cause of death and invalidity in the whole world. Stem cells and products of their secretion find wide application in treatment of vascular diseases, including critical ischaemia of the lower limbs. Erythropoietin promotes an increase in the angiogenic potential of stem cells. The authors examined the therapeutic potential of a biomedical cellular product (mesenchymal stem cells and products of their secretion) and mesenchymal stem cells with erythropoietin on the processes of restoration of vessels in the hind legs of Wistar male rats following induction of lower limb critical ischaemia.

Mesenchymal stem cells were derived from the bone marrow of male Wistar rats. Critical ischaemia of hind legs was modulated by transaction of the femoral artery. The parameters of microcirculation in the foot were assessed with the help of laser Doppler flowmetry. In the blood serum and crural muscles by means of solid-phase enzyme immunoassay we examined the levels of cytokines, growth factors, and persistent metabolites of nitrogen oxide – nitrites. Muscles morphology and the number of blood vessels were assessed by the findings of histological examination.

It was shown that the biomedical cellular product alone and in combination with erythropoietin stimulated angiogenesis. The results of Doppler flowmetry revealed restoration of the parameters of microcirculation in the lower limb by 35-75% of the baseline values. Besides, we observed a decrease of muscle necrosis, connective tissue proliferation, and an increase in the number of the vessels supplying the muscles in the experimental groups. It was also determined that the biomedical cellular product influenced the levels of cytokines in blood serum and crural muscles. Hence, the obtained findings proved the therapeutic potential of the biomedical cellular product in critical ischaemia of lower limbs.

KEY WORDS: lower limb critical ischaemia, mesenchymal stem cells, conditioned medium, erythropoietin, microcirculation, angiogenesis.

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