Di Campli C, Piscaglia A C, Pierelli L, Rutella S, Bonanno G, Alison M R, Mariotti A, Vecchio F M, Nestola M, Monego G, Michetti F, Mancuso S, Pola P, Leone G, Gasbarrini G, Gasbarrini A
Department of Internal Medicine, Catholic University of Rome, Rome, Italy.
Dig Liver Dis. 2004 Sep;36(9):603-13. doi: 10.1016/j.dld.2004.03.017.
Several studies have demonstrated that bone marrow contains a subpopulation of stem cells capable of participating in the hepatic regenerative process, even if some reports indicate quite a low level of liver repopulation by human stem cells in the normal and transiently injured liver.
In order to overcome the low engraftment levels seen in previous models, we tried the direct intraperitoneal administration of human cord blood stem cells, using a model of hepatic damage induced by allyl alcohol in NOD/SCID mice.
We designed a protocol based on stem cell infusion following liver damage in the absence of irradiation. Flow cytometry, histology, immunohistochemistry and RT-PCR for human hepatic markers were performed to monitor human cell engraftment.
Human stem cells were able to transdifferentiate into hepatocytes, to improve liver regeneration after damage and to reduce the mortality rate both in both protocols, even if with qualitative and quantitative differences in the transdifferentiation process.
We demonstrated for the first time that the intraperitoneal administration of stem cells can guarantee a rapid liver engraftment. Moreover, the new protocol based on stem cell infusion following liver damage in the absence of irradiation may represent a step forward for the clinical application of stem cell transplantation.
多项研究表明,骨髓中含有能够参与肝脏再生过程的干细胞亚群,尽管一些报告指出,在正常和短暂受损的肝脏中,人类干细胞对肝脏的再填充水平相当低。
为了克服先前模型中观察到的低植入水平,我们使用烯丙醇诱导NOD/SCID小鼠肝损伤的模型,尝试直接腹腔注射人脐带血干细胞。
我们设计了一种在无辐射情况下肝脏损伤后进行干细胞输注的方案。进行流式细胞术、组织学、免疫组织化学和人肝脏标志物的逆转录聚合酶链反应以监测人类细胞植入情况。
在两种方案中,人类干细胞都能够转分化为肝细胞,改善损伤后的肝脏再生并降低死亡率,尽管在转分化过程中存在定性和定量差异。
我们首次证明腹腔注射干细胞可以保证快速的肝脏植入。此外,基于无辐射情况下肝脏损伤后干细胞输注的新方案可能代表干细胞移植临床应用向前迈进了一步。