背景:肝细胞癌(HCC)的发病率和死亡率都在上升。目前的治疗策略效果有限,主要是由于疾病的复杂原因和严重的耐药性。鉴于人脐带间充质干细胞(hUC-MSCs)研究的最新进展,关于继续使用干细胞移植治疗肿瘤存在争议。因此,本研究旨在探讨hUC-MSCs在HCC治疗中的作用。
结果:在DEN/TCPOBOP诱导的小鼠肝癌模型中,HUC-MSCs数量增加(10.75±1.50),与DMSO组比较(7.25±1.71)。此外,hUC-MSCs组肝脏指数(0.21±0.06)大于DMSO组(0.09±0.01)。免疫组织化学(IHC)分析显示,虽然hUC-MSCs不改变Foxp3表达,它们显著刺激Ki67表达,指示肿瘤细胞增殖增加。此外,免疫荧光(IF)研究显示hUC-MSCs增加CD8+T细胞计数而不影响巨噬细胞数量.值得注意的是,颗粒酶B表达几乎检测不到。我们观察到hUC-MSC组(109.66±0.38pg/ml)的血清IL-18水平高于DMSO组(91.14±4.37pg/ml)。相反,相对于DMSO组(97.38±9.08pg/ml),hUC-MSC组(63.00±0.53pg/ml)中IL-1β水平降低。
结论:根据这项研究,hUC-MSCs促进肝脏肿瘤的生长。因此,我们提出hUC-MSCs不适合治疗HCC,因为它们表现出临床上禁止的异常。
BACKGROUND: Hepatocellular carcinoma (HCC) is experiencing a concerning rise in both incidence and mortality rates. Current therapeutic strategies are limited in their effectiveness, largely due to the complex causes of the disease and significant levels of drug resistance. Given the latest developments in human umbilical cord mesenchymal stem cells (hUC-
MSCs) research, there is a debate over the continued use of stem cell transplantation for treating tumors. Consequently, this study seeks to explore the role of hUC-
MSCs in the management of HCC.
RESULTS: HUC-MSCs increased the number (10.75 ± 1.50) in the DEN/TCPOBOP-induced mice hepatoma model, compared with DMSO group (7.25 ± 1.71). Moreover, the liver index in hUC-
MSCs group (0.21 ± 0.06) was greater than that in DMSO group (0.09 ± 0.01). Immunohistochemical (IHC) analysis revealed that while hUC-
MSCs did not alter Foxp3 expression, they significantly stimulated Ki67 expression, indicative of increased tumor cellular proliferation. Additionally, immunofluorescence (IF) studies showed that hUC-MSCs increased CD8+ T cell counts without affecting macrophage numbers. Notably, granzyme B expression remained nearly undetectable. We observed that serum IL-18 levels were higher in the hUC-MSCs group (109.66 ± 0.38 pg/ml) compared to the DMSO group (91.14 ± 4.37 pg/ml). Conversely, IL-1β levels decreased in the hUC-MSCs group (63.00 ± 0.53 pg/ml) relative to the DMSO group (97.38 ± 9.08 pg/ml).
CONCLUSIONS: According to this study, hUC-
MSCs promoted the growth of liver tumors. Therefore, we proposed that hUC-MSCs are not suitable for treating HCC, as they exhibit clinically prohibited abnormalities.