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您的检索式：作者名="Timur Fatkhudinov"
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| 1 | Multipotent stromal cells stimulate liver regeneration by influencing the macrophage polarization in rat显示文摘AIM To investigate the influence of the umbilical cordderived multipotent stromal cells(MSCs) on recovery of the liver after the subtotal resection, that is, removal of 80% of the organ mass, a renowned model of the small-for-size liver remnant syndrome. METHODS The MSCs were obtained from the intervascular tissue of umbilical cords, dissected from rat fetuses, by the explant culture technique. The vital labeling of MSCs with РКН26 was carried out on the 3 rd passage. The subtotal resection was performed on male Sprague-Dawley rats. The experimental group animals received a transplant 106 MSCs infused into the spleen. Hepatocyte proliferation was assessed by counting of either mitotic figures or Ki67-positive cells in microscopic images. MSC differentiation was assessed with antibodies to hepatocyte-specific marker cytokeratin 18(CK18), cholangiocyte-specific protein CK19, smooth muscle cell-specific protein α-SMA, the endothelial cell marker CD31, or the active fibroblast marker FAPα. Total macrophages of the liver were selectively stained in cryosections incubated with antiCD68 antibodies(1:100, Abcam), while the M2 a and M2 c macrophage populations were selectively stained with anti-CD206 antibodies. Expression of interleukin and growth factor genes was evaluated with PCR-RT.RESULTS Intrasplenic allogeneic transplantation of the umbilical cord-derived multipotent stromal cells stimulates reparative processes within the residual liver tissue after subtotal resection(removal of 80% of the organ mass), as indicated by increased rates of hepatocyte proliferation and accelerated organ mass recovery. These effects may result from paracrine influence of the transplanted cells on the resident macrophage population of the liver. The transplantation favors polarization of macrophages to M2 phenotype(the M2-polarized macrophages specifically express CD206; they are known to suppress inflammation and support tissue repair). No differentiation of the transplanted cells into any of the liver cell types have been observed in the study.CONCLUSION We found no direct evidence for the paracrine effect of MSCs on liver regeneration after the subtotal liver resection in rats. However, the paracrine mechanism of the therapeutic activity of transplanted MSC is indirectly indicated by a decrease in the total number of CD68 + macrophages and an increase in the proportion of M2 pro-repair macrophages in the regenerating liver as compared to animals in which the transplantation was only mimicked. | Andrey Elchaninov Timur Fatkhudinov Natalia Usman Irina Arutyunyan Andrey Makarov Anastasia Lokhonina Irina Eremina Viktor Surovtsev Dmitry Goldshtein Galina Bolshakova Valeria Glinkina Gennady Sukhikh | 2018 | World Journal of Hepatology2018，10，2： | 2 |
| 2 | Regenerative medicine of pancreatic islets显示文摘The pancreas became one of the first objects of regenerative medicine,since other possibilities of dealing with the pancreatic endocrine insufficiency were clearly exhausted.The number of people living with diabetes mellitus is currently approaching half a billion,hence the crucial relevance of new methods to stimulate regeneration of the insulin-secretingβ-cells of the islets of Langerhans.Natural restrictions on the islet regeneration are very tight;nevertheless,the islets are capable of physiological regeneration viaβ-cell self-replication,direct differentiation of multipotent progenitor cells and spontaneousα-toβ-orδ-toβ-cell conversion(trans-differentiation).The existing preclinical models ofβ-cell dysfunction or ablation(induced surgically,chemically or genetically)have significantly expanded our understanding of reparative regeneration of the islets and possible ways of its stimulation.The ultimate goal,sufficient level of functional activity ofβ-cells or their substitutes can be achieved by two prospective broad strategies:β-cell replacement andβ-cell regeneration.The“regeneration”strategy aims to maintain a preserved population ofβ-cells through in situ exposure to biologically active substances that improveβ-cell survival,replication and insulin secretion,or to evoke the intrinsic adaptive mechanisms triggering the spontaneous non-β-toβ-cell conversion.The“replacement”strategy implies transplantation ofβ-cells(as non-disintegrated pancreatic material or isolated donor islets)orβ-like cells obtained ex vivo from progenitors or mature somatic cells(for example,hepatocytes orα-cells)under the action of small-molecule inducers or by genetic modification.We believe that the huge volume of experimental and clinical studies will finally allow a safe and effective solution to a seemingly simple goal-restoration of the functionally activeβ-cells,the innermost hope of millions of people globally. | Irina V Arutyunyan Timur Kh Fatkhudinov Andrey V Makarov Andrey V Elchaninov Gennady T Sukhikh | 2020 | World Journal of Gastroenterology2020，26，22： | 2 |
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