El Baz Hanan, Demerdash Zeinab, Kamel Manal, Atta Shimaa, Salah Faten, Hassan Salwa, Hammam Olfat, Khalil Heba, Bayoumi Ali
From the Immunology Department, Theodor Bilharz Research Institute, Giza, Egypt.
Exp Clin Transplant. 2019 Apr;17(2):251-258. doi: 10.6002/ect.2017.0249. Epub 2018 Oct 19.
Liver transplantation is the well-known treatment for chronic liver diseases; however, postoperative complications and lack of donors continue to be limitations with this treatment. Investigating new modalities for treatment of chronic liver illness is a must. In the present study, we aimed to clarify the effects of an in vitro hepatocyte-differentiated human unrestricted somatic stem cell transplant as a new cell-based therapy in an experimental model of chronic liver failure.
Human umbilical cord blood-derived unrestricted somatic stem cells were isolated, cultured, propagated, and characterized. Cells were directed to differentiate into hepatocyte-like cells. An animal model of carbon tetrachloride cirrhotic liver failure was prepared, and the human in vitro differentiated unrestricted somatic stem cells were transplanted into the experimental model. Animals that did not receive transplant served as the pathologic control group. Animals were euthanized 12 weeks after transplant, and liver functions and histopathology were assessed.
Compared with the pathologic control group, the transplant group showed improvements in levels of alanine aminotransferase, aspartate aminotransferase, albumin, and bilirubin. Histopathologic examination of the transplant group also showed improvements in hydropic degeneration and fibrosis.
The use of unrestricted somatic stem cells, isolated and propagated from cord blood and then differentiated into hepatocyte-like cells, improved both fibrosis and normal function of cirrhotic livers. These cells could be considered as a line of cell-based therapy in cases of chronic liver disease.
肝移植是治疗慢性肝病的知名方法;然而,术后并发症和供体短缺仍然是这种治疗方法的局限性。研究慢性肝病的新治疗方式势在必行。在本研究中,我们旨在阐明体外肝细胞分化的人未受限体细胞干细胞移植作为一种新型细胞治疗方法在慢性肝衰竭实验模型中的效果。
分离、培养、扩增并鉴定人脐带血来源的未受限体细胞干细胞。将细胞诱导分化为肝细胞样细胞。制备四氯化碳诱导的肝硬化肝衰竭动物模型,并将体外分化的人未受限体细胞干细胞移植到该实验模型中。未接受移植的动物作为病理对照组。移植后12周对动物实施安乐死,并评估肝功能和组织病理学。
与病理对照组相比,移植组的丙氨酸氨基转移酶、天冬氨酸氨基转移酶、白蛋白和胆红素水平有所改善。移植组的组织病理学检查还显示细胞水肿变性和纤维化有所改善。
使用从脐带血中分离、扩增并分化为肝细胞样细胞的未受限体细胞干细胞,可改善肝硬化肝脏的纤维化和正常功能。在慢性肝病病例中,这些细胞可被视为一种细胞治疗方法。