Genes & CellsGenes & Cells2313-18292500-2562Human Stem Cells Institute12039110.23868/gc120391Research ArticleEffects of Dalarginum on proliferation of multipotent mesenchymal stromal cells, dermal fibroblasts, and human osteosarcoma cells in vitroVasilyevA. V-BukharovaT. B-VolkovA. V-VikhrovaE. B-BolshakovaG. B-GoldsteinD. V-Research Institute of Human Morphology of RAMSResearch Centre of Medical Genetics of RAMS1512201494768005012023Copyright © 2014, Eco-Vector2014The aim of this work was to assess in vitro the effect of various doses of Dalarginum and its blocker Naloxone on the proliferation of multipotent mesenchymal stromal cells (MMSC), dermal fibroblasts (FD) and human osteosarcoma cell (line HOS). We used MMSC and FD derived from three donors. The cells were cultured for 3 days with solutions of the test substances at following concentrations: Dalarginum 10 jg/l, 100 jg/l, 1000jg/l; combination of naloxone 0.5 mg/l and Dalarginum, 100 jg/l; combination of Naloxone 3 mg/l and Dalarginum, 100jg/l. Saline was added in the culture medium in the control group. The cells were counted by the end of day 3 of culturing. Dalarginum at 100 jg/l significantly increased the number of MMSC by 19-34 % and decreased the count of cells (line HOS) by 22-34 % compared with the control values. There were no significant differences in cell numbers between the groups with addition of dalarginum at 10jg/l and 1000jg/l as well as significant changes in the number of FD under the influence of the test substances. Dalarginum combined with Naloxone, opioid receptor antagonist, had no impact on the number of cells, which confirmed its receptor-mediated action. The optimum effect of Dalarginum on opioid receptors was observed at100jg/l.opioidsDalarginumNaloxoneproliferationmultipotent mesenchymal stromal cellsdermal fibroblaststumor cells of HOS lineопиоидыДаларгинНалоксонпролиферациямультипотентные мезенхимальные стромальные клеткидермальные фибробластыклетки остеосаркомы линии HOS[Rosen H., Krichevsky A., Polakiewicz R.D. et al. Developmental regulation of proenkephalin gene expression in osteoblasts. Mol. Endocrinol. 1995; 9(11): 1621-31.][Keshet E., Polakiewicz R.D., Itin A. et al. Proenkephalin A is expressed in mesodermal lineages during organogenesis. EMBO J. 1989; 8(10): 2917-23.][Perez-Castrillon J.L., Olmos J.M., Gomez J.J. et al. Expression of opioid receptors in osteoblast-like MG-63 cells, and effects of different opioid agonists on alkaline phosphatase and osteocalcin secretion by these cells. Neuroendocrinology 2000; 72(3): 187-94.][Elhassan A.M., Lindgren J.U., Hultenby K. et al. Methionine-enkephalin in bone and joint tissues. J. Bone Miner. Res. 1998; 13(1): 88-95.][Виноградов В.А. Опиоидный гексапептид - даларгин в патогенетической терапии заболеваний органов пищеварения. Сов. медицина. 1989; 10: 59-63.][Слепушкин В.Д. Энкефалины и регенерация. Бюл. Сиб.отд. АМН СССР 1989; 2: 87-92.][Панькова Т.Д. Доказательства реализации стимулирующего эффекта даларгина на процесс клеточного деления через опиатные рецепторы. Бюл. эксперим. биологии и медицины 1990; 7(110): 96-8.][Бухарова Т.Б. Разработка тканеинженерной конструкции на основе мультипотентных мезенхимальных стромальных клеток жировой ткани, полилактидных носителей и тромбоцитарного геля для восполнения костного дефекта [диссертация]. Москва: ФГБУ «НИ-ИМЧ» РАМН; 2014.][Dominici M., Le Blanc K., Mueller I. et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006; 8(4): 315-7.][Nomura Y., Kawaraguchi Y., Sugimoto H. et al. Effects of morphine and fentanyl on 5-fluorouracil sensitivity in human colon cancer HCT116 cells. J. Anesth. 2014; 28(2): 298-301.][Sadee W., Bilsky E. J., inventors; Compositions and methods in the treatment of bone metabolic disorders. US patent 2007/0197573 Al. 2007 Aug 23.][Ардасенов А.В., Хугаева В.К., Александров П.Н. Микроцир-куляторное русло кожи в условиях воспаления и коррекции методом лимфостимуляции. Москва: Научный Мир; 2004.][Millan M. J., Morris B. J. Long-term blockade of mu-opioid receptors suggests a role in control of ingestive behaviour, body weight and core temperature in the rat. Brain research 1988; 450 (1-2): 247-58.]