关键词: acute liver failure cell biodistribution experimental models of hepatotoxicity galactosoamine human amniotic epithelial cells intraperitoneal injection intravenous injection stem cell therapy

来  源:   DOI:10.3390/ph17040476   PDF(Pubmed)

Abstract:
The route of administration of implanted cells may affect the outcome of cell therapy by directing cell migration to the damaged site. However, the question of the relationship between the route of administration, the efficacy of colonisation of a given organ, and the efficacy of cell therapy has not been resolved. The aim of the study was to localise transplanted intravenously and intraperitoneally human amniotic epithelial cells (hAECs) in the tissues of mice, both healthy and injured, in an animal experimental model of acute liver failure (ALF). Mice intoxicated with D-Galactosamine (D-GalN) at a dose of 150 mg/100 g body weight received D-GalN alone or with a single dose of hAECs administered by different routes. Subsequently, at 6, 24, and 72 h after D-GaIN administration and at 3, 21, and 69 h after hAEC administration, lungs, spleen, liver, and blood were collected from recipient mice. The degree of liver damage and regeneration was assessed based on biochemical blood parameters, histopathological evaluation (H&E staining), and immunodetection of proliferating (Ki67+) and apoptotic (Casp+) cells. The biodistribution of the administered cells was based on immunohistochemistry and the identification of human DNA. It has been shown that after intravenous administration, in both healthy and intoxicated mice, most of the transplanted hAECs were found in the lungs, while after intraperitoneal administration, they were found in the liver. We concluded that a large number of hAECs implanted in the lungs following intravenous administration can exert a therapeutic effect on the damaged liver, while the regenerative effect of intraperitoneally injected hAECs on the liver was very limited due to the relatively lower efficiency of cell engraftment.
摘要:
植入细胞的施用途径可以通过引导细胞迁移到受损部位来影响细胞治疗的结果。然而,行政途径之间的关系问题,特定器官定殖的功效,细胞疗法的疗效尚未解决。该研究的目的是在小鼠组织中定位静脉和腹膜内移植的人羊膜上皮细胞(hAECs),既健康又受伤,在急性肝衰竭(ALF)的动物实验模型中。用剂量为150mg/100g体重的D-半乳糖胺(D-GalN)中毒的小鼠单独接受D-GalN或通过不同途径给予单剂量的hAECs。随后,在D-GaIN给药后6、24和72小时以及hAEC给药后3、21和69小时,肺,脾,脾肝脏,并从受体小鼠收集血液。根据生化血液参数评估肝损伤和再生的程度,组织病理学评估(H&E染色),增殖细胞(Ki67+)和凋亡细胞(Casp+)的免疫检测。施用的细胞的生物分布基于免疫组织化学和人DNA的鉴定。已经表明,静脉给药后,在健康和醉酒的老鼠中,大多数移植的hAECs都是在肺部发现的,而在腹膜内给药后,他们是在肝脏里发现的.我们的结论是,静脉注射后大量植入肺部的hAECs可以对受损的肝脏发挥治疗作用,而由于细胞移植效率相对较低,腹膜内注射hAECs对肝脏的再生作用非常有限。
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