Multipotent stromal cells stimulate liver regeneration by influencing the macrophage polarization in rat

• 作者: Anastasia Lokhonina Andrey Elchaninov Andrey Makarov Dmitry Goldshtein Galina Bolshakova Gennady Sukhikh Irina Arutyunyan Irina Eremina Natalia Usman Timur Fatkhudinov Valeria Glinkina Viktor Surovtsev
• 来源期刊: 世界肝病学杂志：英文版（电子版）
• 学科: 医学
• 关键词: LIVER REGENERATION MULTIPOTENT STROMAL cells MACROPHAGES
• 年，卷（期）: 2018,（2）
• 页码范围: 287-296
• 页数: 10页
• 分类号: R

摘要

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 withРКН26 was carried out on the 3rd 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 proteinα-SMA,the endothelial cell marker CD31,or the active fibroblast marker FAPα.Total macrophages of the liver were selectively stained in cryosections incubated with anti-CD68 antibodies(1:100,Abcam),while the M2a and M2c 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 f