Lykov A P, Bondarenko N A, Poveshchenko O V, Kabakov A V, Surovtseva M A, Kim I I, Kazakov O V, Poveshchenko A F, Iankaĭte E V
Scientific Research Institute of Clinical and Experimental Lymphology, Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia; National Medical Research Centre named after Academician E.N. Meshalkin, Novosibirsk, Russia.
National Medical Research Centre named after Academician E.N. Meshalkin, Novosibirsk, Russia.
Angiol Sosud Khir. 2020;26(3):37-43. doi: 10.33529/ANGIO2020315.
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.
下肢严重缺血是全球范围内导致死亡和残疾的一个原因。干细胞及其分泌产物在包括下肢严重缺血在内的血管疾病治疗中得到广泛应用。促红细胞生成素可促进干细胞血管生成潜能的增加。作者研究了一种生物医学细胞产品（间充质干细胞及其分泌产物）以及添加促红细胞生成素的间充质干细胞对雄性Wistar大鼠下肢严重缺血后后肢血管修复过程的治疗潜力。间充质干细胞取自雄性Wistar大鼠的骨髓。通过切断股动脉来诱发后肢严重缺血。借助激光多普勒血流仪评估足部的微循环参数。通过固相酶免疫测定法检测血清和小腿肌肉中细胞因子、生长因子以及一氧化氮的持久性代谢产物——亚硝酸盐的水平。通过组织学检查结果评估肌肉形态和血管数量。结果表明，单独使用该生物医学细胞产品以及将其与促红细胞生成素联合使用均能刺激血管生成。多普勒血流仪的结果显示，下肢微循环参数恢复至基线值的35% - 75%。此外，我们观察到实验组肌肉坏死减少、结缔组织增生减少，且供应肌肉的血管数量增加。还确定该生物医学细胞产品会影响血清和小腿肌肉中细胞因子的水平。因此，所获得的研究结果证明了该生物医学细胞产品在下肢严重缺血治疗中的潜力。
